Indometacin 500micrograms/5ml oral solution
Prescription only
Requires a prescription from a doctor or prescriber
Oral solution
5ml
Oral
Indometacin, or indomethacin, is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties.
Active ingredients:
Indometacin
No active safety alerts
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
Submit a Yellow Card report to the MHRA
Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
MHRA
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
View Drug Analysis Profile
Suspected adverse reactions reported for Indometacin
Browse all iDAP reports
Interactive Drug Analysis Profiles for all medicines
Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
EMA
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
View EudraVigilance report
Suspected adverse reactions reported for Indometacin
About EudraVigilance
Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
1 branded products available
Show details
Part of the Indocid brand family (generic: Indometacin)
1 products
MHRA licensed products
View all licensed products for Indometacin on the MHRA register
Show details
WHO defined daily dose (DDD)
100 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
Show details
Diclofenac 75mg/1ml solution for injection ampoules
Injection
75mg/1ml
Same therapeutic group
Tolmetin 600mg tablets
Tablet
600mg
Same therapeutic group
Diclofenac 40mg/5ml oral solution
Oral solution
40mg/5ml
Same therapeutic group
Diclofenac 40mg/5ml oral suspension
Oral suspension
40mg/5ml
Same therapeutic group
Diclofenac 10mg dispersible tablets
Tablet
10mg
Same therapeutic group
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
Show details
Loading prescribing data...
Clinical guidelines and formulary information
British National Formulary
Indometacin
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Show details
Pharmacy stock checkers
Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
Show details
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Show details
Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
141 found
Half-life
1 hour
Mechanism
Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase.
Food interactions
2 warnings
Human targets
11 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
100%
Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional,…
Half-life
1 hour
Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2…
Protein binding
90-99%
Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations .
[A177949][L6778]…
[A177949][L6778]…
Volume of distribution
0.34 to 1.57 L/kg
The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals.
[A177964]…
[A177964]…
Metabolism
Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation.
[A177949]…
[A177949]…
Elimination
27 to 115%
Indometacin is eliminated via renal excretion, metabolism, and biliary excretion.…
Clearance
1 to 2.5 mL
In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Indometacin, or indomethacin, is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic properties. NSAIDs consist of agents that are structurally unrelated; the NSAID chemical classification of indometacin is an indole-acetic acid derivative with the chemical name 1- (p-chlorobenzoyl)25-methoxy-2-methylindole-3-acetic acid.[A177871] The pharmacological effect of indometacin is not fully understood, however, it is thought to be mediated through potent and nonselective inhibition of the enzyme cyclooxygenase (COX), which is the main enzyme responsible for catalyzes the rate-limiting step in prostaglandin and thromboxane biosynthesis via the arachidonic acid (AA) pathway. Indometacin was first discovered in 1963 and it was first approved for use in the U.S. by the Food and Drug Administration in 1965, [A486] along with other acetic acid derivatives such as [diclofenac] and [sulindac] that were also developed during the 1960s.[A177871] Since then, indometacin has been extensively studied in clinical trials as one of the most potent NSAIDs in blocking prostaglandin synthesis and was among the first NSAIDs to be used in the symptomatic treatment of migraine and for headaches that eventually became known as “indomethacin-responsive” headache disorders.[A177871]
Most commonly used in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute shoulder pains, and acute gouty arthritis, indometacin is currently available as oral capsules as well as other methods of administration, including rectal and intravenous formulations. Intravenous indometacin is administered to close a hemodynamically significant patent ductus arteriosus, as indicated by clinical evidence, in premature infants.[L10553] Ophthalmic indometacin has been studied and used in the symptomatic treatment of postoperative ocular inflammation and pain and/or complications after cataract surgery. Although deemed effective in reducing ocular inflammation in clinical studies, topical NSAIDs were also associated with a potential reduction in corneal sensitivity accompanied by an increased risk of superficial punctate keratitis and subjective symptoms of discomfort, including pain, burning or pricking, or a tingling sensation after instillation into the cul‐de‐sac.[A177949]
Most commonly used in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute shoulder pains, and acute gouty arthritis, indometacin is currently available as oral capsules as well as other methods of administration, including rectal and intravenous formulations. Intravenous indometacin is administered to close a hemodynamically significant patent ductus arteriosus, as indicated by clinical evidence, in premature infants.[L10553] Ophthalmic indometacin has been studied and used in the symptomatic treatment of postoperative ocular inflammation and pain and/or complications after cataract surgery. Although deemed effective in reducing ocular inflammation in clinical studies, topical NSAIDs were also associated with a potential reduction in corneal sensitivity accompanied by an increased risk of superficial punctate keratitis and subjective symptoms of discomfort, including pain, burning or pricking, or a tingling sensation after instillation into the cul‐de‐sac.[A177949]
Properties:
solid
Avg. mass: 357.79 Da
DrugBank indication
Oral indometacin is indicated for symptomatic management of moderate to severe rheumatoid arthritis including acute flares of chronic disease, moderate to severe ankylosing spondylitis, moderate to severe osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.
[A177871][L6778]
Intravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective.
[L10553]
[A177871][L6778]
Intravenous indometacin is indicated to induce closure of a hemodynamically significant patent ductus arteriosus in premature infants weighing between 500 and 1750 g when after 48 hours usual medical management (e.g., fluid restriction, diuretics, digitalis, respiratory support, etc.) is ineffective.
[L10553]
Also known as(289)
{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid
1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
Indometacin
Indometacina
Indometacine
Indometacinum
Indomethacin
1.14.99.1
Dosage forms(59)
Capsule (Oral) — 60.0000 mg
Gel (Cutaneous) — 0.0500 g
Suppository
Capsule, coated pellets (Oral) — 75 mg
Capsule (Oral) — 25.00 MG
Cream (Cutaneous) — 2.500 g
— 0.500 g
Capsule (Oral) — 25.000 mg
Molecular properties(19)
Drug interactions(2023)
Known interactions with other medications. Always consult a healthcare professional.
The risk or severity of adverse effects can be increased when Denosumab is combined with Indomethacin.
Peginterferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Indomethacin.
Interferon alfa-n1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Indomethacin.
Interferon alfa-n3
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Indomethacin.
Peginterferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Indomethacin.
Interferon gamma-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Indomethacin.
Interferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Indomethacin.
Aldesleukin
Unknown severity
The risk or severity of adverse effects can be increased when Aldesleukin is combined with Indomethacin.
Gemtuzumab ozogamicin
Unknown severity
The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Indomethacin.
Pegaspargase
Unknown severity
The risk or severity of adverse effects can be increased when Pegaspargase is combined with Indomethacin.
Interferon beta-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Indomethacin.
Interferon alfacon-1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Rituximab is combined with Indomethacin.
Basiliximab
Unknown severity
The risk or severity of adverse effects can be increased when Basiliximab is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Muromonab is combined with Indomethacin.
Ibritumomab tiuxetan
Unknown severity
The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Indomethacin.
Tositumomab
Unknown severity
The risk or severity of adverse effects can be increased when Tositumomab is combined with Indomethacin.
Alemtuzumab
Unknown severity
The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Alefacept is combined with Indomethacin.
Efalizumab
Unknown severity
The risk or severity of adverse effects can be increased when Efalizumab is combined with Indomethacin.
Antithymocyte immunoglobulin (rabbit)
Unknown severity
The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Indomethacin.
Interferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Indomethacin.
Daclizumab
Unknown severity
The risk or severity of adverse effects can be increased when Daclizumab is combined with Indomethacin.
Phenylalanine
Unknown severity
The risk or severity of adverse effects can be increased when Phenylalanine is combined with Indomethacin.
Bortezomib
Unknown severity
The risk or severity of adverse effects can be increased when Bortezomib is combined with Indomethacin.
Cladribine
Moderate
Indomethacin may increase the immunosuppressive activities of Cladribine.
Carmustine
Unknown severity
The risk or severity of adverse effects can be increased when Carmustine is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Amsacrine is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Bleomycin is combined with Indomethacin.
Chlorambucil
Unknown severity
The risk or severity of adverse effects can be increased when Chlorambucil is combined with Indomethacin.
Raltitrexed
Unknown severity
The risk or severity of adverse effects can be increased when Raltitrexed is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Mitomycin is combined with Indomethacin.
Bexarotene
Unknown severity
The risk or severity of adverse effects can be increased when Bexarotene is combined with Indomethacin.
The risk or severity of adverse effects can be increased when Vindesine is combined with Indomethacin.
Tioguanine
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Tioguanine.
Vinorelbine
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Vinorelbine.
Dexrazoxane
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Dexrazoxane.
Streptozocin
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Streptozocin.
Trifluridine
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Trifluridine.
Gemcitabine
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Gemcitabine.
Teniposide
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Teniposide.
Epirubicin
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Epirubicin.
Chloramphenicol
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Chloramphenicol.
Lenalidomide
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Lenalidomide.
Altretamine
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Altretamine.
Oxaliplatin
Major
The risk or severity of nephrotoxicity can be increased when Oxaliplatin is combined with Indomethacin.
Fluorouracil
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Fluorouracil.
Propylthiouracil
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Propylthiouracil.
Pentostatin
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Pentostatin.
Vinblastine
Unknown severity
The risk or severity of adverse effects can be increased when Indomethacin is combined with Vinblastine.
Showing 50 of 2023 interactions
Food & lifestyle interactions
Avoid Alcohol
Avoid alcohol. Ingestion of alcohol can increase the risk of GI bleeding.
Advice
Take with or without food. Food has no effect on drug absorption. However, food may decrease the extent of gastrointestinal irritation caused by indomethacin.
Toxicity & overdose
Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice.MSDS The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively.
[L6778]
Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage.
[L6778]
The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage.
Antacids may be useful.
[L6778]
[L6778]
Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage.
[L6778]
The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage.
Antacids may be useful.
[L6778]
How it works
Mechanism of action
Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation.[A177871] Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2.[A177871] COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis.[L6778] At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth.[A177880] Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus.[A177880] By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.[L10553]
Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis.[A234429][A234434]
The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis.[L6778] At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth.[A177880] Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus.[A177880] By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.[L10553]
Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis.[A234429][A234434]
Pharmacodynamics
Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation.[L6778] Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength.[L6778] In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.[L6778]
In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment.[L6778] The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity.[A177871] There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.[A177871]
In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment.[L6778] The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity.[A177871] There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.[A177871]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent.
[A177871]
Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration [A177871] and about 90% of the dose is absorbed within 4 hours.
[L6778]
The bioavailability is about 80-90% following rectal administration.
[A177901]
The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state.
[A177901]
Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively.
[A177901]
With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.
[L6778]
[A177871]
Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration [A177871] and about 90% of the dose is absorbed within 4 hours.
[L6778]
The bioavailability is about 80-90% following rectal administration.
[A177901]
The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state.
[A177901]
Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively.
[A177901]
With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.
[L6778]
Half-life
Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase.
[A177949]
Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug.
[A177874][A177949]
The mean half-life of oral indomethacin is estimated to be about 4.5 hours.
[L6778]
The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g.
[L10553]
[A177949]
Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug.
[A177874][A177949]
The mean half-life of oral indomethacin is estimated to be about 4.5 hours.
[L6778]
The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g.
[L10553]
Protein binding
Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations .
[A177949][L6778]
Like other NSAIDs, indometacin is bound to plasma albumin [A177949] but it does not bind to red blood cells.
[A177874]
[A177949][L6778]
Like other NSAIDs, indometacin is bound to plasma albumin [A177949] but it does not bind to red blood cells.
[A177874]
Volume of distribution
The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals.
[A177964]
Indometacin is distributed into the synovial fluid [A177874] and is extensively bound to tissues .
[A177949]
It has been detected in human breast milk [A177874] and placenta.
[L6778]
Although indometacin has been shown to cross the blood-brain barrier (BBB)[L6778], its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB.
[A177949]
[A177964]
Indometacin is distributed into the synovial fluid [A177874] and is extensively bound to tissues .
[A177949]
It has been detected in human breast milk [A177874] and placenta.
[L6778]
Although indometacin has been shown to cross the blood-brain barrier (BBB)[L6778], its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB.
[A177949]
Metabolism
Indometacin undergoes hepatic metabolism involving glucuronidation, O-desmethylation, and N-deacylation.
[A177949]
O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity.
[A177949][L6778]
Unconjugated metabolites are also detected in the plasma.
[L6778]
Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism.
[A177949]
[A177949]
O-desmethyl-indomethacin, N-deschlorobenzoyl-indomethacin, and O-desmethyl-N-deschlorobenzoyl-indomethacin metabolites and their glucuronides are primarily inactive and have no pharmacological activity.
[A177949][L6778]
Unconjugated metabolites are also detected in the plasma.
[L6778]
Its high bioavailability indicates that indometacin is unlikely to be subject to the first-pass metabolism.
[A177949]
Route of elimination
Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis .
[A177949]
The extent of involvement in the enterohepatic circulation ranges from 27 to 115%.
[A177949]
About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin).
[L6778]
[A177949]
The extent of involvement in the enterohepatic circulation ranges from 27 to 115%.
[A177949]
About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin).
[L6778]
Clearance
In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration.
[A177874]
[A177874]
Drug targets(11)
Proteins and enzymes this drug interacts with in the body
Prostaglandin G/H synthase 2
PTGS2
inhibitor
Specific functionenzyme binding
Cellular location
Microsome membrane
General function & pharmacology
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response .
PMID:11939906 PMID:16373578 PMID:19540099 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins .
PMID:11939906 PMID:19540099
In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids .
PMID:27642067
Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response .
PMID:22942274
Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols .
PMID:11034610 PMID:11192938 PMID:9048568 PMID:9261177
Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation .
PMID:12391014
Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) .
PMID:12391014
As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 .
PMID:21206090
In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection .
PMID:26236990
In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) .
PMID:22068350 PMID:26282205
Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity).
During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
PMID:11939906 PMID:16373578 PMID:19540099 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins .
PMID:11939906 PMID:19540099
In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids .
PMID:27642067
Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response .
PMID:22942274
Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols .
PMID:11034610 PMID:11192938 PMID:9048568 PMID:9261177
Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation .
PMID:12391014
Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) .
PMID:12391014
As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 .
PMID:21206090
In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection .
PMID:26236990
In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) .
PMID:22068350 PMID:26282205
Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity).
During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Phospholipase A2, membrane associated
PLA2G2A
inhibitor
Specific functioncalcium ion binding
Cellular location
Secreted
General function & pharmacology
Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration .
PMID:10455175 PMID:10681567 PMID:2925633
Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines .
PMID:10455175 PMID:10681567
Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane .
PMID:10358193 PMID:11694541
Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response .
PMID:25082876
Plays a stem cell regulator role in the intestinal crypt.
Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation.
Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines .
PMID:14998370
Independent of its catalytic activity, acts as a ligand for integrins .
PMID:18635536 PMID:25398877
Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 .
PMID:18635536 PMID:25398877
Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 .
PMID:25398877
Induces cell proliferation in an integrin-dependent manner PMID:18635536
PMID:10455175 PMID:10681567 PMID:2925633
Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines .
PMID:10455175 PMID:10681567
Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane .
PMID:10358193 PMID:11694541
Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response .
PMID:25082876
Plays a stem cell regulator role in the intestinal crypt.
Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation.
Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines .
PMID:14998370
Independent of its catalytic activity, acts as a ligand for integrins .
PMID:18635536 PMID:25398877
Binds to and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 .
PMID:18635536 PMID:25398877
Binds to a site (site 2) which is distinct from the classical ligand-binding site (site 1) and induces integrin conformational changes and enhanced ligand binding to site 1 .
PMID:25398877
Induces cell proliferation in an integrin-dependent manner PMID:18635536
Prostaglandin G/H synthase 2
PTGS2
inhibitor
Specific functionenzyme binding
Cellular location
Microsome membrane
General function & pharmacology
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response .
PMID:11939906 PMID:16373578 PMID:19540099 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins .
PMID:11939906 PMID:19540099
In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids .
PMID:27642067
Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response .
PMID:22942274
Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols .
PMID:11034610 PMID:11192938 PMID:9048568 PMID:9261177
Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation .
PMID:12391014
Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) .
PMID:12391014
As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 .
PMID:21206090
In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection .
PMID:26236990
In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) .
PMID:22068350 PMID:26282205
Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity).
During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
PMID:11939906 PMID:16373578 PMID:19540099 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons .
PMID:16373578 PMID:22942274 PMID:26859324 PMID:27226593 PMID:7592599 PMID:7947975 PMID:9261177
Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins .
PMID:11939906 PMID:19540099
In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids .
PMID:27642067
Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response .
PMID:22942274
Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols .
PMID:11034610 PMID:11192938 PMID:9048568 PMID:9261177
Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation .
PMID:12391014
Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) .
PMID:12391014
As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 .
PMID:21206090
In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection .
PMID:26236990
In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) .
PMID:22068350 PMID:26282205
Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity).
During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Prostaglandin G/H synthase 1
PTGS1
inhibitor
Specific functionheme binding
Cellular location
Microsome membrane
General function & pharmacology
Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins.
The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons .
PMID:7947975
Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable).
Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity)
The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons .
PMID:7947975
Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable).
Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity)
Interferon-induced, double-stranded RNA-activated protein kinase
EIF2AK2
inducer
Specific functionATP binding
Cellular location
Cytoplasm
General function & pharmacology
IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection .
PMID:18835251 PMID:19189853 PMID:19507191 PMID:21072047 PMID:21123651 PMID:22381929 PMID:22948139 PMID:23229543
Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 .
PMID:19189853 PMID:21123651 PMID:22948139 PMID:23229543
Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) .
PMID:11836380 PMID:19189853 PMID:19840259 PMID:20171114 PMID:21710204 PMID:23115276 PMID:23399035
Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 .
PMID:11836380 PMID:19229320 PMID:22214662
In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation .
PMID:20395957
Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs .
PMID:22948139 PMID:23084476 PMID:23372823
Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 .
PMID:10848580 PMID:15121867 PMID:15229216
Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) .
PMID:20685959
Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) .
PMID:20685959
Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes .
PMID:22801494
Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity)
PMID:18835251 PMID:19189853 PMID:19507191 PMID:21072047 PMID:21123651 PMID:22381929 PMID:22948139 PMID:23229543
Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 .
PMID:19189853 PMID:21123651 PMID:22948139 PMID:23229543
Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) .
PMID:11836380 PMID:19189853 PMID:19840259 PMID:20171114 PMID:21710204 PMID:23115276 PMID:23399035
Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 .
PMID:11836380 PMID:19229320 PMID:22214662
In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation .
PMID:20395957
Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs .
PMID:22948139 PMID:23084476 PMID:23372823
Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 .
PMID:10848580 PMID:15121867 PMID:15229216
Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) .
PMID:20685959
Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) .
PMID:20685959
Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes .
PMID:22801494
Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity)
Metabolizing enzymes(6)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP2C19Cytochrome P450 2C19
substrate
inhibitor
CYP2C9Cytochrome P450 2C9
substrate
CES1Liver carboxylesterase 1
substrate
UGT1A9UDP-glucuronosyltransferase 1A9
substrate
UGT1A1UDP-glucuronosyltransferase 1A1
substrate
inhibitor
UGT2B7UDP-glucuronosyltransferase 2B7
substrate
inhibitor
Transporters(15)
Proteins that transport this drug across cell membranes
ATP-binding cassette sub-family C member 3
ABCC3
inhibitor
Specific functionABC-type bile acid transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes .
PMID:10359813 PMID:11581266 PMID:15083066
Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) .
PMID:11581266 PMID:15083066
Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable).
Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells PMID:10359813 PMID:11581266
PMID:10359813 PMID:11581266 PMID:15083066
Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) .
PMID:11581266 PMID:15083066
Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable).
Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells PMID:10359813 PMID:11581266
ATP-binding cassette sub-family C member 4
ABCC4
inhibitor
Specific function15-hydroxyprostaglandin dehydrogenase (NAD+) activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins .
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
ATP-binding cassette sub-family C member 6
ABCC6
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Basal cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of glutathione conjugates such as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS) (in vitro), and an anionic cyclopentapeptide endothelin antagonist, BQ-123 .
PMID:11880368 PMID:12414644
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Does not appear to actively transport drugs outside the cell.
Confers low levels of cellular resistance to etoposide, teniposide, anthracyclines and cisplatin PMID:12414644
PMID:11880368 PMID:12414644
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Does not appear to actively transport drugs outside the cell.
Confers low levels of cellular resistance to etoposide, teniposide, anthracyclines and cisplatin PMID:12414644
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Multidrug resistance-associated protein 1
ABCC1
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates export of organic anions and drugs from the cytoplasm .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export .
PMID:9281595
Hydrolyzes ATP with low efficiency .
PMID:16230346
Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation .
PMID:17050692
Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export .
PMID:36070769
Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway .
PMID:36070769
Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity).
Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells PMID:9426231
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export .
PMID:9281595
Hydrolyzes ATP with low efficiency .
PMID:16230346
Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation .
PMID:17050692
Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export .
PMID:36070769
Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway .
PMID:36070769
Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity).
Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells PMID:9426231
Solute carrier organic anion transporter family member 1A2
SLCO1A2
substrate
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane .
PMID:19129463 PMID:7557095
Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) .
PMID:11159893 PMID:12568656 PMID:19129463 PMID:23918469 PMID:25560245 PMID:9539145
Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision .
PMID:25560245
Involved in the uptake of clinically used drugs .
PMID:17301733 PMID:20686826 PMID:27777271
Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) .
PMID:19129463 PMID:20358049
Also transports prostaglandin E2 .
PMID:19129463
Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:19129463 PMID:7557095
Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) .
PMID:11159893 PMID:12568656 PMID:19129463 PMID:23918469 PMID:25560245 PMID:9539145
Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision .
PMID:25560245
Involved in the uptake of clinically used drugs .
PMID:17301733 PMID:20686826 PMID:27777271
Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) .
PMID:19129463 PMID:20358049
Also transports prostaglandin E2 .
PMID:19129463
Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Solute carrier family 22 member 6
SLC22A6
substrate
inhibitor
Specific functionalpha-ketoglutarate transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate .
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
Organic anion transporter 3
SLC22A8
inhibitor
Specific functionorganic anion transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient .
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
ATP-binding cassette sub-family C member 2
ABCC2
substrate
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates .
PMID:10220572 PMID:10421658 PMID:11500505 PMID:16332456
Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification .
PMID:10421658
Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 .
PMID:11500505
Transports sulfated bile salt such as taurolithocholate sulfate .
PMID:16332456
Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors .
PMID:10220572 PMID:11500505 PMID:12441801
Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine PMID:10220572 PMID:11500505
PMID:10220572 PMID:10421658 PMID:11500505 PMID:16332456
Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification .
PMID:10421658
Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 .
PMID:11500505
Transports sulfated bile salt such as taurolithocholate sulfate .
PMID:16332456
Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors .
PMID:10220572 PMID:11500505 PMID:12441801
Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine PMID:10220572 PMID:11500505
ATP-binding cassette sub-family C member 11
ABCC11
inhibitor
Specific functionABC-type bile acid transporter activity
Cellular location
Cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Plays a role in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides, including cAMP and cGMP .
PMID:12764137 PMID:15537867
Mediates the ATP-dependent efflux of a range of physiological lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates, such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate .
PMID:15537867 PMID:16359813 PMID:25896536
Plays a role in the transport of earwax components .
PMID:16444273 PMID:19383836
Participates in the secretion of odorants and their precursors from the apocrine sweat glands, including the secretion of glutamine conjugates, as well as the Cys-Gly-(S) conjugates of 3-methyl-3-sulfanyl-hexanol .
PMID:19710689
Involved in the cellular extrusion of nucleotide analogs, hence confering resistance to various drugs, including clinically relevant drugs such as 5-fluorouracil (5-FU) and methotrexate PMID:12764137 PMID:15537867 PMID:25896536
PMID:12764137 PMID:15537867
Mediates the ATP-dependent efflux of a range of physiological lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates, such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate .
PMID:15537867 PMID:16359813 PMID:25896536
Plays a role in the transport of earwax components .
PMID:16444273 PMID:19383836
Participates in the secretion of odorants and their precursors from the apocrine sweat glands, including the secretion of glutamine conjugates, as well as the Cys-Gly-(S) conjugates of 3-methyl-3-sulfanyl-hexanol .
PMID:19710689
Involved in the cellular extrusion of nucleotide analogs, hence confering resistance to various drugs, including clinically relevant drugs such as 5-fluorouracil (5-FU) and methotrexate PMID:12764137 PMID:15537867 PMID:25896536
Solute carrier family 22 member 11
SLC22A11
inhibitor
Specific functionorganic anion transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds .
PMID:10660625 PMID:11907186 PMID:15037815 PMID:15102942 PMID:15291761 PMID:15576633 PMID:17229912 PMID:18501590 PMID:26277985 PMID:28027879
May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus .
PMID:12409283
Maybe also be involved in placental urate homeostasis .
PMID:17229912
Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates .
PMID:15037815 PMID:17229912
Organic anion glutarate acts as conteranion for E1S renal uptake .
PMID:15037815 PMID:17229912
Possible transport mode may also include DHEA-S/E1S exchange .
PMID:28027879
Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) .
PMID:17229912
Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion .
PMID:11907186
Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A .
PMID:10660625 PMID:26277985
Mediates the unidirectional efflux of glutamate and aspartate .
PMID:28027879
Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S PMID:26277985
PMID:10660625 PMID:11907186 PMID:15037815 PMID:15102942 PMID:15291761 PMID:15576633 PMID:17229912 PMID:18501590 PMID:26277985 PMID:28027879
May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus .
PMID:12409283
Maybe also be involved in placental urate homeostasis .
PMID:17229912
Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates .
PMID:15037815 PMID:17229912
Organic anion glutarate acts as conteranion for E1S renal uptake .
PMID:15037815 PMID:17229912
Possible transport mode may also include DHEA-S/E1S exchange .
PMID:28027879
Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) .
PMID:17229912
Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion .
PMID:11907186
Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A .
PMID:10660625 PMID:26277985
Mediates the unidirectional efflux of glutamate and aspartate .
PMID:28027879
Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S PMID:26277985
Hepatic sodium/bile acid cotransporter
SLC10A1
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
As a major transporter of conjugated bile salts from plasma into the hepatocyte, it plays a key role in the enterohepatic circulation of bile salts necessary for the solubilization and absorption of dietary fat and fat-soluble vitamins .
PMID:14660639 PMID:24867799 PMID:34060352 PMID:8132774
It is strictly dependent on the extracellular presence of sodium .
PMID:14660639 PMID:24867799 PMID:34060352 PMID:8132774
It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate .
PMID:14660639 PMID:34060352
Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation PMID:33222321
PMID:14660639 PMID:24867799 PMID:34060352 PMID:8132774
It is strictly dependent on the extracellular presence of sodium .
PMID:14660639 PMID:24867799 PMID:34060352 PMID:8132774
It exhibits broad substrate specificity and transports various bile acids, such as taurocholate, cholate, as well as non-bile acid organic compounds, such as estrone sulfate .
PMID:14660639 PMID:34060352
Works collaboratively with the ileal transporter (NTCP2), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation PMID:33222321
Solute carrier family 22 member 7
SLC22A7
substrate
Specific functionalpha-ketoglutarate transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Functions as a Na(+)-independent bidirectional multispecific transporter .
PMID:11327718 PMID:18216183 PMID:21446918 PMID:28945155
Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively .
PMID:11327718 PMID:25904762
Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates .
PMID:11327718 PMID:18216183 PMID:26377792 PMID:28945155
Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways .
PMID:18216183 PMID:26377792
Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood .
PMID:21446918
Involved in renal secretion and possible reabsorption of creatinine .
PMID:25904762 PMID:28945155
Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate .
PMID:11327718 PMID:26377792
Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified PMID:26377792
PMID:11327718 PMID:18216183 PMID:21446918 PMID:28945155
Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively .
PMID:11327718 PMID:25904762
Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates .
PMID:11327718 PMID:18216183 PMID:26377792 PMID:28945155
Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways .
PMID:18216183 PMID:26377792
Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood .
PMID:21446918
Involved in renal secretion and possible reabsorption of creatinine .
PMID:25904762 PMID:28945155
Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate .
PMID:11327718 PMID:26377792
Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified PMID:26377792
Solute carrier organic anion transporter family member 1B1
SLCO1B1
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
Bile salt export pump
ABCB11
substrate
Specific functionABC-type bile acid transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner .
PMID:15791618 PMID:16332456 PMID:18985798 PMID:19228692 PMID:20010382 PMID:20398791 PMID:22262466 PMID:24711118 PMID:29507376 PMID:32203132
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts .
PMID:16332456
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion PMID:15901796 PMID:18245269
PMID:15791618 PMID:16332456 PMID:18985798 PMID:19228692 PMID:20010382 PMID:20398791 PMID:22262466 PMID:24711118 PMID:29507376 PMID:32203132
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts .
PMID:16332456
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion PMID:15901796 PMID:18245269
Carriers(1)
Proteins that carry this drug through the body
Albumin
ALB
Specific functionantioxidant activity
Cellular location
Secreted
General function & pharmacology
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc .
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Biological pathways(1)
Scientific references(12)
Lucas S.
The Pharmacology of Indomethacin.
Headache
2016 Feb56(2):436-46. doi: 10.1111/head.12769. Epub 2016 Feb 11
Helleberg L.
Clinical Pharmacokinetics of indomethacin.
Clinical Pharmacokinetics
1981 Jul-Aug6(4):245-58. doi: 10.2165/00003088-198106040-00001
Nalamachu S., Wortmann R.
Role of indomethacin in acute pain and inflammation management: a review of the literature.
Postgrad Medicine
2014 Jul126(4):92-7. doi: 10.3810/pgm.2014.07.2787
Pacifici G.M.
Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure.
Paediatr Drugs
2013 Oct15(5):363-76. doi: 10.1007/s40272-013-0031-7
Jensen K.M., Grenabo L.
Bioavailability of Indomethacin after Intramuscular Injection and Rectal Administration of Solution and Suppositories.
Acta Pharmacologica et Toxicologica
198557(5):322-327. doi: 10.1111/j.1600-0773.1985.tb00052.x
Weber M., Kodjikian L., Kruse F.E., Zagorski Z., Allaire C.M.
Efficacy and safety of indomethacin 0.
1% eye drops compared with ketorolac 0
5% eye drops in the management of ocular inflammation after cataract surgery. Acta Ophthalmol. 2013 Feb91(1):e15-21. doi: 10.1111/j.1755-3768.2012.02520.x. Epub 2012 Sep 12
Alvan G., Orme M., Bertilsson L., Ekstrand R., Palmer L.
Pharmacokinetics of indomethacin.
Clinical Pharmacology & Therapeutics
197518(3):364-373. doi: 10.1002/cpt1975183364
Ricciotti E., FitzGerald G.A.
Prostaglandins and inflammation.
Arterioscler Thromb Vasc Biological
2011 May31(5):986-1000. doi: 10.1161/ATVBAHA.110.207449
Rouzer C.A., Marnett L.J.
Cyclooxygenases: structural and functional insights.
Journal Lipid Research
2009 Apr50 Suppl:S29-34. doi: 10.1194/jlr.R800042-JLR200. Epub 2008 Oct 23
HART F.D., BOARDMAN P.L.
Indomethacin: A New Non-steroid Anti-inflammatory Agent.
British Medical Journal
19632(5363):965-970. doi: 10.1136/bmj.2.5363.965
Brunelli C., Amici C., Angelini M., Fracassi C., Belardo G., Santoro M.G.
The non-steroidal anti-inflammatory drug indomethacin activates the eIF2alpha kinase PKR, causing a translational block in human colorectal cancer cells.
Biochemistry Journal
2012 Apr 15443(2):379-86. doi: 10.1042/BJ20111236
Amici C., La Frazia S., Brunelli C., Balsamo M., Angelini M., Santoro M.G.
Inhibition of viral protein translation by indomethacin in vesicular stomatitis virus infection: role of eIF2alpha kinase PKR.
Cell Microbiology
2015 Sep17(9):1391-404. doi: 10.1111/cmi.12446. Epub 2015 May 13
ATC classification(6 codes)
ATC S01CC02
ATC M01AB51
ATC S01BC01
ATC M02AA23
ATC M01AB01
ATC C01EB03
Affected organisms(1)
Humans and other mammals
International brands(12)
Salt forms(1)
Indomethacin sodium(DBSALT001435)
Experimental properties(6)
Protein Data Bank entries(24)
Commercial products(292)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Indomethacin
Matched from: Indometacin
Synonym match
95% confidenceAdditional database identifiers
Drugs Product Database (DPD)
10126
ChemSpider
3584
BindingDB
17638
PDB
IMN
Guide to Pharmacology
1909
ZINC
ZINC000000601283
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9605
GenAtlas
PTGS2
GeneCards
PTGS2
GenBank Gene Database
L15326
GenBank Protein Database
291988
Guide to Pharmacology
1376
UniProt Accession
PGH2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9031
GenAtlas
PLA2G2A
GeneCards
PLA2G2A
GenBank Gene Database
M22430
GenBank Protein Database
190889
Guide to Pharmacology
1417
UniProt Accession
PA2GA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9604
GenAtlas
PTGS1
GeneCards
PTGS1
GenBank Gene Database
M31822
GenBank Protein Database
387018
Guide to Pharmacology
1375
UniProt Accession
PGH1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9605
GenAtlas
PTGS2
GeneCards
PTGS2
GenBank Gene Database
L15326
GenBank Protein Database
291988
Guide to Pharmacology
1376
UniProt Accession
PGH2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9604
GenAtlas
PTGS1
GeneCards
PTGS1
GenBank Gene Database
M31822
GenBank Protein Database
387018
Guide to Pharmacology
1375
UniProt Accession
PGH1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9437
GeneCards
EIF2AK2
Guide to Pharmacology
2016
UniProt Accession
E2AK2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:20149
GeneCards
PTGR2
GenBank Gene Database
AY346133
GenBank Protein Database
37912002
UniProt Accession
PTGR2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9236
GenAtlas
PPARG
GeneCards
PPARG
GenBank Gene Database
U79012
GenBank Protein Database
1711117
Guide to Pharmacology
595
UniProt Accession
PPARG_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4323
GenAtlas
GLO1
GeneCards
GLO1
GenBank Gene Database
D13315
GenBank Protein Database
219664
UniProt Accession
LGUL_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4502
GeneCards
PTGDR2
GenBank Gene Database
AB008535
GenBank Protein Database
4204216
Guide to Pharmacology
339
UniProt Accession
PD2R2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9232
GenAtlas
PPARA
GeneCards
PPARA
GenBank Gene Database
L02932
GenBank Protein Database
307341
Guide to Pharmacology
593
UniProt Accession
PPARA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:386
GenAtlas
AKR1C3
GeneCards
AKR1C3
GenBank Gene Database
S68288
GenBank Protein Database
4261711
Guide to Pharmacology
1382
UniProt Accession
AK1C3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1863
GenAtlas
CES1
GeneCards
CES1
GenBank Gene Database
M73499
Guide to Pharmacology
2592
UniProt Accession
EST1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12541
GeneCards
UGT1A9
GenBank Gene Database
S55985
GenBank Protein Database
7690346
UniProt Accession
UD19_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12530
GeneCards
UGT1A1
GenBank Gene Database
M57899
GenBank Protein Database
184473
Guide to Pharmacology
2990
UniProt Accession
UD11_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12554
GeneCards
UGT2B7
GenBank Gene Database
J05428
GenBank Protein Database
340080
UniProt Accession
UD2B7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:54
GenAtlas
ABCC3
GeneCards
ABCC3
GenBank Gene Database
AB010887
GenBank Protein Database
3132270
UniProt Accession
MRP3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:55
GenAtlas
ABCC4
GeneCards
ABCC4
GenBank Gene Database
AF071202
GenBank Protein Database
3335173
Guide to Pharmacology
782
UniProt Accession
MRP4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:57
GeneCards
ABCC6
GenBank Gene Database
AF076622
GenBank Protein Database
3928849
UniProt Accession
MRP6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:51
GenAtlas
ABCC1
GeneCards
ABCC1
GenBank Gene Database
L05628
GenBank Protein Database
1835659
Guide to Pharmacology
779
UniProt Accession
MRP1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10956
GeneCards
SLCO1A2
GenBank Gene Database
U21943
GenBank Protein Database
885978
Guide to Pharmacology
1219
UniProt Accession
SO1A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10970
GenAtlas
hROAT1
GeneCards
SLC22A6
GenBank Gene Database
AF057039
GenBank Protein Database
3831566
Guide to Pharmacology
1025
UniProt Accession
S22A6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10972
GeneCards
SLC22A8
GenBank Gene Database
AF097491
GenBank Protein Database
4378059
Guide to Pharmacology
1027
UniProt Accession
S22A8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:53
GenAtlas
ABCC2
GeneCards
ABCC2
GenBank Gene Database
U63970
GenBank Protein Database
1764162
Guide to Pharmacology
780
UniProt Accession
MRP2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14639
GeneCards
ABCC11
GenBank Gene Database
AY040219
GenBank Protein Database
15027829
UniProt Accession
MRP8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:18120
GenAtlas
SLC22A11
GeneCards
SLC22A11
GenBank Gene Database
AB026116
GenBank Protein Database
7707622
Guide to Pharmacology
1030
UniProt Accession
S22AB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10905
GeneCards
SLC10A1
GenBank Gene Database
L21893
GenBank Protein Database
410214
Guide to Pharmacology
959
UniProt Accession
NTCP_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10971
GeneCards
SLC22A7
GenBank Gene Database
AF097518
GenBank Protein Database
5001689
UniProt Accession
S22A7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:42
GenAtlas
ABCB11
GeneCards
ABCB11
GenBank Gene Database
AF091582
GenBank Protein Database
3873243
Guide to Pharmacology
778
UniProt Accession
ABCBB_HUMAN
International reference pricing
17 formulations
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
From $0.09/capsule
To $642.60/vial
Apo-Indomethacin 25 mg Capsule
$0.09/capsule
Novo-Methacin 25 mg Capsule
$0.09/capsule
Nu-Indo 25 mg Capsule
$0.09/capsule
Apo-Indomethacin 50 mg Capsule
$0.16/capsule
Novo-Methacin 50 mg Capsule
$0.16/capsule
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
3 active patents
9089471
United States
Approved 28 Jul 2015 · Expires 23 Apr 2030
4 years
8992982
United States
Approved 31 Mar 2015 · Expires 23 Apr 2030
4 years
8734847
United States
Approved 27 May 2014 · Expires 23 Apr 2030
4 years
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 27 days ago(8 Mar 2026)