Diclofenac 50mg/5ml oral solution
Prescription only
Requires a prescription from a doctor or prescriber
Oral solution
50mg/5ml
Oral
Diclofenac is a phenylacetic acid derivative and non-steroidal anti-inflammatory drug (NSAID).[label] NSAIDs inhibit cyclooxygenase (COX)-1 and-2 which are the enzyme responsible for producing prostaglandins (PGs).
Active ingredients:
Diclofenac sodium
No active safety alerts
Official documents, adverse reaction reporting, and safety monitoring
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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.
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Suspected adverse reactions reported for Diclofenac sodium
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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.
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Suspected adverse reactions reported for Diclofenac sodium
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1 branded products available
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Part of the Acoflam brand family (generic: Diclofenac sodium)
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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
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Clinical guidelines and formulary information
British National Formulary
Diclofenac sodium
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.
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Supply & product information
Official product databases and supply status monitoring
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Codes for healthcare professionals and prescribing systems
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These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
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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
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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
147 found
Half-life
2 h
Mechanism
Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for product…
Food interactions
2 warnings
Human targets
2 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
60%
Diclofenac is completely absorbed from the GI tract but likely undergoes significant first pass metabolism with only 60% of the drug reaching systemic circulation unchanged [label,A178633,A180694].…
Half-life
2 h
The terminal half-life of diclofenac is approximately 2 h, however the apparent half-life including all metabolites is 25.8-33 h.[label,A180694]
Protein binding
99.7%
Diclofenac is over 99.7% bound to serum proteins, primarily albumin.
[A178633]…
[A178633]…
Volume of distribution
5-10 L
Diclofenac has a total volume of distribution of 5-10 L or 0.1-0.2…
Metabolism
Diclofenac undergoes oxidative metabolism to hydroxy metabolites as well as conjugation to glucuronic acid, sulfate, and taurine.[label,A178633]…
Elimination
60-70%
Diclofenac is mainly eliminated via metabolism.
[A178633][A180694]
Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces.…
[A178633][A180694]
Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces.…
Clearance
16 L/h
Diclofenac has a plasma clearance 16 L/h.
[A180694]
[A180694]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Vet approved
Small molecule
About this compound
Diclofenac is a phenylacetic acid derivative and non-steroidal anti-inflammatory drug (NSAID).[label] NSAIDs inhibit cyclooxygenase (COX)-1 and-2 which are the enzyme responsible for producing prostaglandins (PGs). PGs contribute to inflammation and pain signalling. Diclofenac, like other NSAIDs, is often used as first line therapy for acute and chronic pain and inflammation from a variety of causes. Diclofenac was the product of rational drug design based on the structures of [phenylbutazone], [mefenamic acid], and [indomethacin].[A180796] The addition of two chlorine groups in the ortho position of the phenyl ring locks the ring in maximal torsion which appears to be related to increased potency. It is often used in combination with [misoprostol] to prevent NSAID-induced gastric ulcers. Diclofenac was first approved by the FDA in July 1988 under the trade name Voltaren, marketed by Novartis (previously Ciba-Geigy).[L7360]
Properties:
View FDA drug labelsolid
Avg. mass: 296.15 Da
DrugBank indication
Diclofenac is indicated for use in the treatment of pain and inflammation from varying sources including inflammatory conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, as well as injury-related inflammation due to surgery and physical trauma. It is often used in combination with [misoprostol] as a gastro-protective agent in patients with high risk of developing NSAID-induced ulcers.
Also known as(228)
[2-(2,6-dichloroanilino)phenyl]acetic acid
2-((2,6-dichlorophenyl)amino)benzeneacetic acid
Diclofenac
Diclofenac acid
Diclofenaco
Diclofenacum
1.14.99.1
COX-2
Dosage forms(368)
Solution (Ophthalmic) — 1.000 mg
Gel (Cutaneous) — 10 MG
Gel (Cutaneous) — 11600 MG
Injection, solution (Intravenous)
Injection, solution (Parenteral) — 25 MG/ML
Injection, solution (Parenteral) — 50 MG/ML
Injection, solution (Parenteral) — 75 MG/ML
Gel (Topical) — 1 mg/1g
Molecular properties(19)
Drug interactions(1863)
Known interactions with other medications. Always consult a healthcare professional.
Reserpine may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Progesterone
Moderate
Progesterone may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Chlorpromazine
Moderate
Chlorpromazine may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Cimetidine
Moderate
Cimetidine may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Bosentan may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Glyburide may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Ursodeoxycholic acid
Moderate
Ursodeoxycholic acid may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Cholic Acid
Moderate
Cholic Acid may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Fusidic acid
Moderate
Fusidic acid may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Simeprevir
Moderate
Simeprevir may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Lenvatinib
Moderate
Lenvatinib may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Letermovir
Moderate
The metabolism of Diclofenac can be decreased when combined with Letermovir.
Valinomycin
Moderate
Valinomycin may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Erythromycin
Unknown severity
The serum concentration of Diclofenac can be increased when it is combined with Erythromycin.
Pralsetinib
Moderate
Pralsetinib may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Peginterferon alfa-2b
Unknown severity
The serum concentration of Diclofenac can be increased when it is combined with Peginterferon alfa-2b.
Leflunomide
Unknown severity
The serum concentration of Diclofenac can be decreased when it is combined with Leflunomide.
Teriflunomide
Unknown severity
The serum concentration of Diclofenac can be decreased when it is combined with Teriflunomide.
Amlodipine
Moderate
The metabolism of Diclofenac can be decreased when combined with Amlodipine.
The risk or severity of hypertension can be increased when Midodrine is combined with Diclofenac.
Isoetharine
Unknown severity
The risk or severity of hypertension can be increased when Isoetharine is combined with Diclofenac.
Norepinephrine
Unknown severity
The risk or severity of hypertension can be increased when Norepinephrine is combined with Diclofenac.
Phenylpropanolamine
Unknown severity
The risk or severity of hypertension can be increased when Phenylpropanolamine is combined with Diclofenac.
Droperidol
Unknown severity
The risk or severity of hypertension can be increased when Droperidol is combined with Diclofenac.
The risk or severity of hypertension can be increased when Doxapram is combined with Diclofenac.
The risk or severity of hypertension can be increased when Diclofenac is combined with Linezolid.
Metaraminol
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Metaraminol.
Furazolidone
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Furazolidone.
Nicergoline
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Nicergoline.
Methoxamine
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Methoxamine.
Propiomazine
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Propiomazine.
The risk or severity of hypertension can be increased when Diclofenac is combined with Minaprine.
Orciprenaline
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Orciprenaline.
Phenmetrazine
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Phenmetrazine.
Pseudoephedrine
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Pseudoephedrine.
The risk or severity of hypertension can be increased when Diclofenac is combined with Ritodrine.
Remifentanil
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Remifentanil.
Bitolterol
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Bitolterol.
Oxymetazoline
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Oxymetazoline.
Diethylpropion
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Diethylpropion.
Naratriptan
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Naratriptan.
Isoprenaline
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Isoprenaline.
Arbutamine
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Arbutamine.
Desflurane
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Desflurane.
Isocarboxazid
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Isocarboxazid.
Lisdexamfetamine
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Lisdexamfetamine.
The risk or severity of hypertension can be increased when Diclofenac is combined with Fenoterol.
Pirbuterol
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Pirbuterol.
Ephedra sinica root
Unknown severity
The risk or severity of hypertension can be increased when Diclofenac is combined with Ephedra sinica root.
The risk or severity of hypertension can be increased when Diclofenac is combined with Ephedrine.
Showing 50 of 1863 interactions
Food & lifestyle interactions
Avoid Alcohol
Avoid excessive or chronic alcohol consumption. Co-administration with alcohol may increase the risk of gastrointestinal side effects, such as ulceration.
Take With Food
Take with food. Food reduces gastric irritation.
Toxicity & overdose
Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain, and gastrointestinal bleeding.[label] Hypertension, acute renal failure, respiratory depression and coma occur rarely. In case of overdose, provide supportive care and consider inducing emesis and administering activated charcoal if overdose occurred less than 4 hours prior.
How it works
Mechanism of action
Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for production of prostaglandin (PG) G2 which is the precursor to other PGs.[label,T116] These molecules have broad activity in pain and inflammation and the inhibition of their production is the common mechanism linking each effect of diclofenac.
PGE2 is the primary PG involved in modulation of nociception.[A179023] It mediates peripheral sensitization through a variety of effects.[T116,A179023] PGE2 activates the Gq-coupled EP1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE2 also activates the EP4 receptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE2 act via EP3 to increase sensitivity to bradykinin and via EP2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP2 receptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI2 is known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.
PGI2 and PGE2 contribute to acute inflammation via their IP and EP2 receptors.[T116,A179044] Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGE2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.T116 PGD2 plays a role in the activation of endothelial cell release of cytokines through its DP1 receptor.[A179044] PGI2 and PGE2 modulate T-helper cell activation and differentiation through IP, EP2, and EP4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.
PGE2 can cross the blood-brain barrier and act on excitatory Gq EP3 receptors on thermoregulatory neurons in the hypothalamus.T116 This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE2 thereby reducing the activity of these neurons.
PGE2 is the primary PG involved in modulation of nociception.[A179023] It mediates peripheral sensitization through a variety of effects.[T116,A179023] PGE2 activates the Gq-coupled EP1 receptor leading to increased activity of the inositol trisphosphate/phospholipase C pathway. Activation of this pathway releases intracellular stores of calcium which directly reduces action potential threshold and activates protein kinase C (PKC) which contributes to several indirect mechanisms. PGE2 also activates the EP4 receptor, coupled to Gs, which activates the adenylyl cyclase/protein kinase A (AC/PKA) signaling pathway. PKA and PKC both contribute to the potentiation of transient receptor potential cation channel subfamily V member 1 (TRPV1) potentiation, which increases sensitivity to heat stimuli. They also activate tetrodotoxin-resistant sodium channels and inhibit inward potassium currents. PKA further contributes to the activation of the P2X3 purine receptor and sensitization of T-type calcium channels. The activation and sensitization of depolarizing ion channels and inhibition of inward potassium currents serve to reduce the intensity of stimulus necessary to generate action potentials in nociceptive sensory afferents. PGE2 act via EP3 to increase sensitivity to bradykinin and via EP2 to further increase heat sensitivity. Central sensitization occurs in the dorsal horn of the spinal cord and is mediated by the EP2 receptor which couples to Gs. Pre-synaptically, this receptor increases the release of pro-nociceptive neurotransmitters glutamate, CGRP, and substance P. Post-synaptically it increases the activity of AMPA and NMDA receptors and produces inhibition of inhibitory glycinergic neurons. Together these lead to a reduced threshold of activating, allowing low intensity stimuli to generate pain signals. PGI2 is known to play a role via its Gs-coupled IP receptor although the magnitude of its contribution varies. It has been proposed to be of greater importance in painful inflammatory conditions such as arthritis. By limiting sensitization, both peripheral and central, via these pathways NSAIDs can effectively reduce inflammatory pain.
PGI2 and PGE2 contribute to acute inflammation via their IP and EP2 receptors.[T116,A179044] Similarly to β adrenergic receptors these are Gs-coupled and mediate vasodilation through the AC/PKA pathway. PGE2 also contributes by increasing leukocyte adhesion to the endothelium and attracts the cells to the site of injury.T116 PGD2 plays a role in the activation of endothelial cell release of cytokines through its DP1 receptor.[A179044] PGI2 and PGE2 modulate T-helper cell activation and differentiation through IP, EP2, and EP4 receptors which is believed to be an important activity in the pathology of arthritic conditions. By limiting the production of these PGs at the site of injury, NSAIDs can reduce inflammation.
PGE2 can cross the blood-brain barrier and act on excitatory Gq EP3 receptors on thermoregulatory neurons in the hypothalamus.T116 This activation triggers an increase in heat-generation and a reduction in heat-loss to produce a fever. NSAIDs prevent the generation of PGE2 thereby reducing the activity of these neurons.
Pharmacodynamics
Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever.[label,T116] It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach.
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Diclofenac is completely absorbed from the GI tract but likely undergoes significant first pass metabolism with only 60% of the drug reaching systemic circulation unchanged [label,A178633,A180694]. Many topical formulations are absorbed percutaneous and produce clinically significant plasma concentrations. Absorption is dose proportional over the range of 25-150 mg.
[A178633]
Tmax varies between formulations with the oral solution reaching peak plasma concentrations in 10-40min, the enteric coated tablet in 1.5-2h, and the sustained- and extended-release formulations prolonging Tmax even further.
Administration with food has no significant effects on AUC but does delay Tmax to 2.5-12h.
[A178633][A180694]
[A178633]
Tmax varies between formulations with the oral solution reaching peak plasma concentrations in 10-40min, the enteric coated tablet in 1.5-2h, and the sustained- and extended-release formulations prolonging Tmax even further.
Administration with food has no significant effects on AUC but does delay Tmax to 2.5-12h.
[A178633][A180694]
Half-life
The terminal half-life of diclofenac is approximately 2 h, however the apparent half-life including all metabolites is 25.8-33 h.[label,A180694]
Protein binding
Diclofenac is over 99.7% bound to serum proteins, primarily albumin.
[A178633]
It is undergoes limited binding to lipoproteins as well with 1.1% bound to HDL, 0.3% to LDL, and 0.15% to VLDL.
[A178633]
It is undergoes limited binding to lipoproteins as well with 1.1% bound to HDL, 0.3% to LDL, and 0.15% to VLDL.
Volume of distribution
Diclofenac has a total volume of distribution of 5-10 L or 0.1-0.2 L/kg.
[A178633]
The volume of the central compartment is 0.04 L/kg.
[A180694]
Diclofenac distributes to the synovial fluid reaching peak concentration 2-4h after administration.
[A178633]
There is limited crossing of the blood brain barrier and cerebrospinal fluid concentrations only reach 8.22% of plasma concentrations. Doses of 50 mg delivered via intramuscular injection produced no detectable diclofenac concentrations in breast milk, however metabolite concentrations were not investigated. Diclofenac has been shown to cross the placenta in mice and rats but human data is unavailable.
[A180694]
[A178633]
The volume of the central compartment is 0.04 L/kg.
[A180694]
Diclofenac distributes to the synovial fluid reaching peak concentration 2-4h after administration.
[A178633]
There is limited crossing of the blood brain barrier and cerebrospinal fluid concentrations only reach 8.22% of plasma concentrations. Doses of 50 mg delivered via intramuscular injection produced no detectable diclofenac concentrations in breast milk, however metabolite concentrations were not investigated. Diclofenac has been shown to cross the placenta in mice and rats but human data is unavailable.
[A180694]
Metabolism
Diclofenac undergoes oxidative metabolism to hydroxy metabolites as well as conjugation to glucuronic acid, sulfate, and taurine.[label,A178633] The primary metabolite is 4'-hydroxy diclofenac which is generated by CYP2C9. This metabolite is very weakly active with one thirtieth the activity of diclofenac. Other metabolites include 3'-hydroxy diclofenac, 3'-hydroxy-4'methoxy diclofenac, 4',5-dihydroxy diclofenac, an acylglucuronide conjugate, and other conjugate metabolites.
Route of elimination
Diclofenac is mainly eliminated via metabolism.
[A178633][A180694]
Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces. No significant enterohepatic recycling occurs.
[A178633][A180694]
Of the total dose, 60-70% is eliminated in the urine and 30% is eliminated in the feces. No significant enterohepatic recycling occurs.
Clearance
Diclofenac has a plasma clearance 16 L/h.
[A180694]
[A180694]
Drug targets(2)
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)
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)
Metabolizing enzymes(14)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP2C9Cytochrome P450 2C9
substrate
CYP2C19Cytochrome P450 2C19
substrate
CYP1A2Cytochrome P450 1A2
substrate
CYP2C8Cytochrome P450 2C8
substrate
UGT2B7UDP-glucuronosyltransferase 2B7
substrate
CYP3A4Cytochrome P450 3A4
substrate
inhibitor
CYP2B6Cytochrome P450 2B6
substrate
CYP2C18Cytochrome P450 2C18
substrate
CYP2E1Cytochrome P450 2E1
inhibitor
UGT1A3UDP-glucuronosyltransferase 1A3
substrate
UGT1A9UDP-glucuronosyltransferase 1A9
substrate
UGT2B4UDP-glucuronosyltransferase 2B4
substrate
ALOX5Polyunsaturated fatty acid 5-lipoxygenase
potentiator
PLA2G2APhospholipase A2, membrane associated
inhibitor
Transporters(13)
Proteins that transport this drug across cell membranes
Solute carrier family 22 member 6
SLC22A6
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
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
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
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)
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
Solute carrier organic anion transporter family member 1C1
SLCO1C1
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane .
PMID:12351693 PMID:18566113 PMID:19129463
Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases .
PMID:18566113
Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases .
PMID:18566113
Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency .
PMID:12351693 PMID:19129463
Transports T4 and E1S in a pH-insensitive manner .
PMID:19129463
Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain PMID:30296914
PMID:12351693 PMID:18566113 PMID:19129463
Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases .
PMID:18566113
Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases .
PMID:18566113
Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency .
PMID:12351693 PMID:19129463
Transports T4 and E1S in a pH-insensitive manner .
PMID:19129463
Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain PMID:30296914
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
Sodium channel protein type 4 subunit alpha
SCN4A
inhibitor
Specific functionvoltage-gated sodium channel activity
Cellular location
Cell membrane
General function & pharmacology
Pore-forming subunit of Nav1.4, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient.
The influx of Na+ ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues .
PMID:12766226 PMID:15318338 PMID:16890191 PMID:17898326 PMID:18690054 PMID:19347921 PMID:25707578 PMID:26659129 PMID:26700687 PMID:29992740 PMID:30190309
Highly expressed in skeletal muscles, Nav1.4 generates the action potential crucial for muscle contraction PMID:16890191 PMID:19347921 PMID:25707578 PMID:26659129 PMID:26700687
The influx of Na+ ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues .
PMID:12766226 PMID:15318338 PMID:16890191 PMID:17898326 PMID:18690054 PMID:19347921 PMID:25707578 PMID:26659129 PMID:26700687 PMID:29992740 PMID:30190309
Highly expressed in skeletal muscles, Nav1.4 generates the action potential crucial for muscle contraction PMID:16890191 PMID:19347921 PMID:25707578 PMID:26659129 PMID:26700687
Acid-sensing ion channel 1
ASIC1
inhibitor
Specific functionligand-gated sodium channel activity
Cellular location
Cell membrane
General function & pharmacology
Forms voltage-independent, pH-gated trimeric sodium channels that act as postsynaptic excitatory receptors in the nervous system, playing a crucial role in regulating synaptic plasticity, learning, and memory .
PMID:21036899 PMID:32915133 PMID:34319232
Upon extracellular pH drop this channel elicits transient, fast activating, and completely desensitizing inward currents .
PMID:21036899
Displays high selectivity for sodium ions but can also permit the permeation of other cations .
PMID:21036899
Regulates more or less directly intracellular calcium concentration and CaMKII phosphorylation, and thereby the density of dendritic spines. Modulates neuronal activity in the circuits underlying innate fear (By similarity)
PMID:21036899 PMID:32915133 PMID:34319232
Upon extracellular pH drop this channel elicits transient, fast activating, and completely desensitizing inward currents .
PMID:21036899
Displays high selectivity for sodium ions but can also permit the permeation of other cations .
PMID:21036899
Regulates more or less directly intracellular calcium concentration and CaMKII phosphorylation, and thereby the density of dendritic spines. Modulates neuronal activity in the circuits underlying innate fear (By similarity)
Potassium voltage-gated channel subfamily KQT member 2
KCNQ2
agonist
Specific functionankyrin binding
Cellular location
Cell membrane
General function & pharmacology
Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability .
PMID:24277843 PMID:28793216 PMID:9836639
M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers .
PMID:10781098 PMID:14534157 PMID:32884139 PMID:37857637 PMID:9836639
The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs .
PMID:14534157 PMID:28793216 PMID:9836639
KCNQ2-KCNQ3 M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) .
PMID:28793216
M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) .
PMID:28793216
Suppressed by activation of the muscarinic acetylcholine receptor CHRM1 PMID:10684873 PMID:10713961
PMID:24277843 PMID:28793216 PMID:9836639
M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers .
PMID:10781098 PMID:14534157 PMID:32884139 PMID:37857637 PMID:9836639
The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs .
PMID:14534157 PMID:28793216 PMID:9836639
KCNQ2-KCNQ3 M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) .
PMID:28793216
M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) .
PMID:28793216
Suppressed by activation of the muscarinic acetylcholine receptor CHRM1 PMID:10684873 PMID:10713961
Potassium voltage-gated channel subfamily KQT member 3
KCNQ3
agonist
Specific functioncalmodulin binding
Cellular location
Cell membrane
General function & pharmacology
Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability .
PMID:16319223 PMID:27564677 PMID:28793216 PMID:9872318
M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers .
PMID:14534157 PMID:16319223 PMID:27564677 PMID:9872318
The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs .
PMID:14534157 PMID:16319223 PMID:28793216
M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) .
PMID:28793216
M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) .
PMID:28793216
Suppressed by activation of M1 muscarinic acetylcholine receptors .
PMID:10713961
KCNQ3 also associates with KCNQ5 to form a functional channel in vitro and may also contribute to the M-current in brain PMID:11159685
PMID:16319223 PMID:27564677 PMID:28793216 PMID:9872318
M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers .
PMID:14534157 PMID:16319223 PMID:27564677 PMID:9872318
The native M-current has a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs .
PMID:14534157 PMID:16319223 PMID:28793216
M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) .
PMID:28793216
M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) .
PMID:28793216
Suppressed by activation of M1 muscarinic acetylcholine receptors .
PMID:10713961
KCNQ3 also associates with KCNQ5 to form a functional channel in vitro and may also contribute to the M-current in brain PMID:11159685
ATP-dependent translocase ABCB1
ABCB1
inducer
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
Carriers(2)
Proteins that carry this drug through the body
Transthyretin
TTR
Specific functionhormone activity
Cellular location
Secreted
General function & pharmacology
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
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(16)
Kearney P.M., Baigent C., Godwin J., Halls H., Emberson J.R., Patrono C.
Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.
British Medical Journal
2006332(7553):1302-1308. doi: 10.1136/bmj.332.7553.1302
Solomon D.H., Avorn J., Sturmer T., Glynn R.J., Mogun H., Schneeweiss S.
Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: High‐risk subgroups and time course of risk.
Arthritis & Rheumatism
200654(5):1378-1389. doi: 10.1002/art.21887
FitzGerald G.A., Patrono C.
The Coxibs, Selective Inhibitors of Cyclooxygenase-2.
New England Journal of Medicine
2001345(6):433-442. doi: 10.1056/nejm200108093450607
Graham D.J.
COX-2 Inhibitors, Other NSAIDs, and Cardiovascular Risk.
Journal of the American Medical Association
2006296(13):1653. doi: 10.1001/jama.296.13.jed60058
Brater D.C.
Renal Effects of Cyclooxygyenase-2-Selective Inhibitors.
Journal of Pain and Symptom Management
200223(4):S15-S20. doi: 10.1016/s0885-3924(02)00370-6
Gan T.J.
Diclofenac: an update on its mechanism of action and safety profile.
Curr Medicine Research Opinion
2010 Jul26(7):1715-31. doi: 10.1185/03007995.2010.486301
Davies N.M., Anderson K.E.
Clinical pharmacokinetics of diclofenac.
Therapeutic insights and pitfalls
Clin Pharmacokinet. 1997 Sep33(3):184-213. doi: 10.2165/00003088-199733030-00003
Todd P.A., Sorkin E.M.
Diclofenac sodium.
A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy
Drugs. 1988 Mar35(3):244-85. doi: 10.2165/00003495-198835030-00004
Kuehl G.E., Lampe J.W., Potter J.D., Bigler J.
Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes.
Drug Metabolism and Disposition
2005 Jul33(7):1027-35. doi: 10.1124/dmd.104.002527. Epub 2005 Apr 20
Chen L., Yang G., Grosser T.
Prostanoids and inflammatory pain.
Prostaglandins Other Lipid Mediat
2013 Jul-Aug104-105:58-66. doi: 10.1016/j.prostaglandins.2012.08.006. Epub 2012 Sep 3
Hirata T., Narumiya S.
Prostanoids as regulators of innate and adaptive immunity.
Advanced Immunology
2012116:143-74. doi: 10.1016/B978-0-12-394300-2.00005-3
Sallmann A.R.
The history of diclofenac.
The American Journal of Medicine
198680(4):29-33. doi: 10.1016/0002-9343(86)90076-8
Bort R., Mace K., Boobis A., Gomez-Lechon M.J., Pfeifer A., Castell J.
Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways.
Biochemical Pharmacology
199958(5):787-796. doi: 10.1016/s0006-2952(99)00167-7
Yan Z., Li J., Huebert N., Caldwell G.W., Du Y., Zhong H.
Detection of a novel reactive metabolite of diclofenac: evidence for CYP2C9-mediated bioactivation via arene oxides.
Drug Metabolism and Disposition
2005 Jun33(6):706-13. doi: 10.1124/dmd.104.003095. Epub 2005 Mar 11
Boerma J.S., Vermeulen N.P., Commandeur J.N.
One-electron oxidation of diclofenac by human cytochrome P450s as a potential bioactivation mechanism for formation of 2'-(glutathion-S-yl)-deschloro-diclofenac.
Chemistry Biological Interact
2014 Jan 25207:32-40. doi: 10.1016/j.cbi.2013.11.001. Epub 2013 Nov 15
Kamimura H., Ito S., Nozawa K., Nakamura S., Chijiwa H., Nagatsuka S., Kuronuma M., Ohnishi Y., Suemizu H., Ninomiya S.
Formation of the accumulative human metabolite and human-specific glutathione conjugate of diclofenac in TK-NOG chimeric mice with humanized livers.
Drug Metabolism and Disposition
2015 Mar43(3):309-16. doi: 10.1124/dmd.114.061689. Epub 2014 Dec 11
ATC classification(6 codes)
ATC S01CC01
ATC S01BC03
ATC M01AB55
ATC M02AA15
ATC M01AB05
ATC D11AX18
Affected organisms(1)
Humans and other mammals
International brands(9)
Salt forms(5)
Diclofenac deanol(DBSALT003116)
Diclofenac diethylamine(DBSALT001945)
Diclofenac epolamine(DBSALT001398)
Diclofenac potassium(DBSALT000864)
Diclofenac sodium(DBSALT000466)
Experimental properties(4)
Protein Data Bank entries(20)
Commercial products(1149)
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)
Additional database identifiers
Drugs Product Database (DPD)
2013
Drugs Product Database (DPD)
1205
Drugs Product Database (DPD)
20061
ChemSpider
2925
BindingDB
13066
PDB
DIF
Guide to Pharmacology
2714
ZINC
ZINC000000001281
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:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_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:2596
GenAtlas
CYP1A2
GeneCards
CYP1A2
GenBank Gene Database
Z00036
Guide to Pharmacology
1319
UniProt Accession
CP1A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_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:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2620
GeneCards
CYP2C18
GenBank Gene Database
M61853
Guide to Pharmacology
1327
UniProt Accession
CP2CI_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2631
GeneCards
CYP2E1
GenBank Gene Database
J02625
GenBank Protein Database
181360
Guide to Pharmacology
1330
UniProt Accession
CP2E1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12535
GeneCards
UGT1A3
GenBank Gene Database
M84127
GenBank Protein Database
340135
UniProt Accession
UD13_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:12553
GeneCards
UGT2B4
GenBank Gene Database
Y00317
GenBank Protein Database
37589
UniProt Accession
UD2B4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:435
GenAtlas
ALOX5
GeneCards
ALOX5
GenBank Gene Database
J03600
GenBank Protein Database
187193
Guide to Pharmacology
1385
UniProt Accession
LOX5_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:12405
GenAtlas
TTR
GeneCards
TTR
GenBank Gene Database
K02091
GenBank Protein Database
189582
Guide to Pharmacology
2851
UniProt Accession
TTHY_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: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: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: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: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: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:13819
GeneCards
SLCO1C1
GenBank Gene Database
AF260704
GenBank Protein Database
7839587
UniProt Accession
SO1C1_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
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10591
GenAtlas
SCN4A
GeneCards
SCN4A
GenBank Gene Database
M81758
GenBank Protein Database
338213
Guide to Pharmacology
581
UniProt Accession
SCN4A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:100
GenAtlas
ACCN2
GeneCards
ASIC1
GenBank Gene Database
U78180
GenBank Protein Database
1871168
Guide to Pharmacology
684
UniProt Accession
ASIC1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6296
GenAtlas
KCNQ2
GeneCards
KCNQ2
GenBank Gene Database
D82346
GenBank Protein Database
1841342
Guide to Pharmacology
561
UniProt Accession
KCNQ2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6297
GenAtlas
KCNQ3
GeneCards
KCNQ3
GenBank Gene Database
AF071491
Guide to Pharmacology
562
UniProt Accession
KCNQ3_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
International reference pricing
25 formulations
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
From $0.20/tablet
To $2.73/ml
Apo-Diclo 25 mg Enteric-Coated Tablet
$0.20/tablet
Novo-Difenac 25 mg Enteric-Coated Tablet
$0.20/tablet
Nu-Diclo 25 mg Enteric-Coated Tablet
$0.20/tablet
Pms-Diclofenac 25 mg Enteric-Coated Tablet
$0.20/tablet
Sandoz Diclofenac 25 mg Enteric-Coated Tablet
$0.20/tablet
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
39 active patents, 9 expired
11351133
United States
Approved 7 Jun 2022 · Expires 20 Feb 2035
8y 10m
11344520
United States
Approved 31 May 2022 · Expires 20 Feb 2035
8y 10m
8546450
United States
Approved 1 Oct 2013 · Expires 9 Aug 2030
4y 4m
9180095
United States
Approved 10 Nov 2015 · Expires 23 Apr 2030
4 years
9186328
United States
Approved 17 Nov 2015 · Expires 23 Apr 2030
4 years
The earliest active patent expires June 2026. Generic versions may become available after this date.
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)