Sulfasalazine 125mg/5ml oral suspension
Prescription only
Requires a prescription from a doctor or prescriber
Oral suspension
125mg/5ml
Oral
Sulfasalazine is an anti-inflammatory drug structurally related to salicylates and other non-steroidal anti-inflammatory drugs.
Active ingredients:
Sulfasalazine
1 safety notice
Safety information for pregnancy and breastfeeding
Pregnancy
Withdrawal of the drug appears to reverse these effects.[L39065]
There are no adequate and well-controlled studies of sulfasalazine in pregnant women.
There are no adequate and well-controlled studies of sulfasalazine in pregnant women.
Reproduction studies have been performed in rats and rabbits at doses up to 6 times the human maintenance dose of 2 g/day based on body surface area and have revealed no evidence of impaired female fertility or harm to the fetus due to sulfasalazine.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.[L39065]
There have been case reports of neural tube defects (NTDs) in infants born to mothers who were exposed to sulfasalazine during pregnancy, but the role of sulfasalazine in these defects has not been established.
There have been case reports of neural tube defects (NTDs) in infants born to mothers who were exposed to sulfasalazine during pregnancy, but the role of sulfasalazine in these defects has not been established.
However, oral sulfasalazine inhibits the absorption and metabolism of folic acid which may interfere with folic acid supplementation (see Drug Interactions) and diminish the effect of periconceptional folic acid supplementation that has been shown to decrease the risk of NTDs.[L39065]
A national survey evaluated the outcome of pregnancies associated with inflammatory bowel disease (IBD).
A national survey evaluated the outcome of pregnancies associated with inflammatory bowel disease (IBD).
In a group of 186 women treated with sulfasalazine alone or sulfasalazine and concomitant steroid therapy, the incidence of fetal morbidity and mortality was comparable to that for 245 untreated IBD pregnancies as well as to pregnancies in the general population.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
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 Sulfasalazine
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 Sulfasalazine
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
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Part of the Salazopyrin brand family (generic: Sulfasalazine)
1 products
MHRA licensed products
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WHO defined daily dose (DDD)
2 gram
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.
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1g
Same therapeutic group
Mesalazine 300mg/5ml oral suspension
Oral suspension
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Same therapeutic group
Mesalazine 4g modified-release granules sachets sugar free
Granules
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Same therapeutic group
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Granules
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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
Sulfasalazine
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.
NICE clinical guidance(7)
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Updated Oct 2023Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
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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
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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
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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
158 found
Half-life
3.4 hours
Mechanism
Although the exact mechanism of action of sulfasalazine is not fully understood,…
Food interactions
1 warning
Human targets
15 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
15%
Following oral administration of 1 g of sulfasalazine to 9 healthy males, less than 15% of a dose of sulfasalazine is absorbed as the parent drug.…
Half-life
3.4 hours
The observed plasma half-life for intravenous sulfasalazine is 7.6…
Protein binding
99.3%
Sulfasalazine is highly bound to albumin (>99.3%) while sulfapyridine is only about 70% bound to albumin. Acetylsulfapyridine,…
Volume of distribution
1.6 L
Following intravenous injection, the calculated volume of distribution for sulfasalazine was 7.5 ± 1.6 L.
[L39065]
[L39065]
Metabolism
15%
In the intestine, sulfasalazine is metabolized by intestinal bacteria to sulfapyridine and 5-aminosalicylic acid.…
Elimination
Absorbed sulfapyridine and 5-aminosalicylic acid and their metabolites are primarily eliminated in the urine either as free metabolites or as glucuronide conjugates.…
Clearance
1 L/h
The calculated clearance of sulfasalazine following intravenous administration was 1 L/hr.…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Sulfasalazine is an anti-inflammatory drug structurally related to salicylates and other non-steroidal anti-inflammatory drugs. It is indicated for managing inflammatory diseases such as ulcerative colitis and rheumatoid arthritis (RA).[L39065][A255582] Metabolized by intestinal bacteria, sulfasalazine is broken down into [mesalazine] and [sulfapyridine], 2 compounds that carry out the main pharmacological activity of sulfasalazine.[A255582]
Sulfasalazine was first used in 1940 for rheumatic polyarthritis, and has been firmly established itself as one fo the most useful disease-modifying antirheumatic drug (DMARD).[A255582] Compared to the first line treatment of RA like methotrexate, sulfasalazine is almost as efficacious as methotrexate although with slightly less tolerability. However, sulfasalazine has less teratogenic side effects and faster onset of action compared to conventional DMARD.[A255582] Sulfasalazine fell out of favor as the drug of choice for RA due to poorly designed clinical trials in 1950 but regained interest from the clinical community in the late 1970.[A255582]
Although sulfasalazine is only approved by the FDA for ulcerative colitis, research have shown that sulfasalazine is also beneficial for patients with Crohn's disease.[A255592] Meta-analysis of 19 randomized controlled trials indicated that sulfasalazine is superior to placebo in inducing remission; however, with no supported evidence of mucosal healing, sulfasalazine is not FDA-recommmended for treatment of Crohn's disease.[A255597][A255602][A255607]
Sulfasalazine was first used in 1940 for rheumatic polyarthritis, and has been firmly established itself as one fo the most useful disease-modifying antirheumatic drug (DMARD).[A255582] Compared to the first line treatment of RA like methotrexate, sulfasalazine is almost as efficacious as methotrexate although with slightly less tolerability. However, sulfasalazine has less teratogenic side effects and faster onset of action compared to conventional DMARD.[A255582] Sulfasalazine fell out of favor as the drug of choice for RA due to poorly designed clinical trials in 1950 but regained interest from the clinical community in the late 1970.[A255582]
Although sulfasalazine is only approved by the FDA for ulcerative colitis, research have shown that sulfasalazine is also beneficial for patients with Crohn's disease.[A255592] Meta-analysis of 19 randomized controlled trials indicated that sulfasalazine is superior to placebo in inducing remission; however, with no supported evidence of mucosal healing, sulfasalazine is not FDA-recommmended for treatment of Crohn's disease.[A255597][A255602][A255607]
Properties:
solid
Avg. mass: 398.39 Da
DrugBank indication
In the US, sulfasalazine is indicated to treat mild to moderate ulcerative colitis and to prolong the remission period between acute attacks of ulcerative colitis.
[L39065]
Sulfasalazine is also indicated as an adjunct therapy in severe ulcerative colitis.
[L39065]
For the delayed-release tablet formulation, sulfasalazine is also indicated to treat rheumatoid arthritis in pediatric patients who have responded inadequately to salicylates or other nonsteroidal anti-inflammatory drugs or polyarticular-course juvenile rheumatoid arthritis with the same patients' characteristics.
[L39065]
[L39065]
Sulfasalazine is also indicated as an adjunct therapy in severe ulcerative colitis.
[L39065]
For the delayed-release tablet formulation, sulfasalazine is also indicated to treat rheumatoid arthritis in pediatric patients who have responded inadequately to salicylates or other nonsteroidal anti-inflammatory drugs or polyarticular-course juvenile rheumatoid arthritis with the same patients' characteristics.
[L39065]
Also known as(180)
2-Hydroxy-5-((4-((2-pyridinylamino)sulfonyl)phenyl)azo)benzoic acid
2-Hydroxy-5-[4-(pyridin-2-ylsulfamoyl)-phenylazo]-benzoic acid
4-(Pyridyl-2-amidosulfonyl)-3'-carboxy-4'-hydroxyazobenzene
5-((p-(2-Pyridylsulfamoyl)phenyl)azo)salicylic acid
5-(4-(2-Pyridylsulfamoyl)phenylazo)-2-hydroxybenzoic acid
5-(p-(2-Pyridylsulfamyl)phenylazo)salicylic acid
Azopyrin
Salazosulfapiridina
Dosage forms(12)
Tablet (Oral) — 500.000 mg
Tablet, coated (Oral) — 500 mg
Tablet, film coated (Oral) — 500 mg
Tablet, delayed release (Oral) — 500 mg
Suspension (Rectal) — 3 g / 100 mL
Enema (Rectal) — 3 g / 100 mL
Tablet (Oral) — 500 mg
Tablet (Oral)
Molecular properties(19)
Drug interactions(1959)
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 Sulfasalazine.
Peginterferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Sulfasalazine.
Interferon alfa-n1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Sulfasalazine.
Interferon alfa-n3
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Sulfasalazine.
Peginterferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Anakinra is combined with Sulfasalazine.
Interferon gamma-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Sulfasalazine.
Interferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Sulfasalazine.
Aldesleukin
Unknown severity
The risk or severity of adverse effects can be increased when Aldesleukin is combined with Sulfasalazine.
Adalimumab
Unknown severity
The risk or severity of adverse effects can be increased when Adalimumab is combined with Sulfasalazine.
Gemtuzumab ozogamicin
Unknown severity
The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Sulfasalazine.
Pegaspargase
Unknown severity
The risk or severity of adverse effects can be increased when Pegaspargase is combined with Sulfasalazine.
Infliximab
Unknown severity
The risk or severity of adverse effects can be increased when Infliximab is combined with Sulfasalazine.
Interferon beta-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Sulfasalazine.
Interferon alfacon-1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Rituximab is combined with Sulfasalazine.
Basiliximab
Unknown severity
The risk or severity of adverse effects can be increased when Basiliximab is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Muromonab is combined with Sulfasalazine.
Ibritumomab tiuxetan
Unknown severity
The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Sulfasalazine.
Tositumomab
Unknown severity
The risk or severity of adverse effects can be increased when Tositumomab is combined with Sulfasalazine.
Alemtuzumab
Unknown severity
The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Alefacept is combined with Sulfasalazine.
Efalizumab
Unknown severity
The risk or severity of adverse effects can be increased when Efalizumab is combined with Sulfasalazine.
Antithymocyte immunoglobulin (rabbit)
Unknown severity
The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Sulfasalazine.
Interferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Sulfasalazine.
Daclizumab
Unknown severity
The risk or severity of adverse effects can be increased when Daclizumab is combined with Sulfasalazine.
Phenylalanine
Unknown severity
The risk or severity of adverse effects can be increased when Phenylalanine is combined with Sulfasalazine.
Bortezomib
Unknown severity
The risk or severity of adverse effects can be increased when Bortezomib is combined with Sulfasalazine.
Cladribine
Unknown severity
The excretion of Cladribine can be decreased when combined with Sulfasalazine.
Carmustine
Unknown severity
The risk or severity of adverse effects can be increased when Carmustine is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Amsacrine is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Bleomycin is combined with Sulfasalazine.
Chlorambucil
Unknown severity
The risk or severity of adverse effects can be increased when Chlorambucil is combined with Sulfasalazine.
Raltitrexed
Unknown severity
The risk or severity of adverse effects can be increased when Raltitrexed is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Mitomycin is combined with Sulfasalazine.
Bexarotene
Unknown severity
The risk or severity of adverse effects can be increased when Bexarotene is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Vindesine is combined with Sulfasalazine.
Floxuridine
Unknown severity
The risk or severity of adverse effects can be increased when Floxuridine is combined with Sulfasalazine.
Tioguanine
Unknown severity
The risk or severity of adverse effects can be increased when Tioguanine is combined with Sulfasalazine.
Vinorelbine
Unknown severity
The risk or severity of adverse effects can be increased when Vinorelbine is combined with Sulfasalazine.
Dexrazoxane
Unknown severity
The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Sulfasalazine.
The risk or severity of adverse effects can be increased when Sorafenib is combined with Sulfasalazine.
Streptozocin
Unknown severity
The risk or severity of adverse effects can be increased when Streptozocin is combined with Sulfasalazine.
Trifluridine
Unknown severity
The risk or severity of adverse effects can be increased when Trifluridine is combined with Sulfasalazine.
Gemcitabine
Unknown severity
The risk or severity of adverse effects can be increased when Gemcitabine is combined with Sulfasalazine.
Teniposide
Unknown severity
The risk or severity of adverse effects can be increased when Teniposide is combined with Sulfasalazine.
Epirubicin
Unknown severity
The risk or severity of adverse effects can be increased when Epirubicin is combined with Sulfasalazine.
Chloramphenicol
Unknown severity
The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Sulfasalazine.
Lenalidomide
Unknown severity
The risk or severity of adverse effects can be increased when Lenalidomide is combined with Sulfasalazine.
Altretamine
Unknown severity
The risk or severity of adverse effects can be increased when Altretamine is combined with Sulfasalazine.
Showing 50 of 1959 interactions
Food & lifestyle interactions
Advice
Drink plenty of fluids. Inadequate fluid intake is associated with crystalluria and stone formation.
Toxicity & overdose
Two-year oral carcinogenicity studies were conducted in male and female F344/N rats and B6C3F1 mice. Sulfasalazine was tested at 84 (496 mg/m2), 168 (991 mg/m2), and 337.5 (1991 mg/m2) mg/kg/day doses in rats. A statistically significant increase in the incidence of urinary bladder transitional cell papillomas was observed in male rats.
In female rats, two (4%) of the 337.5 mg/kg rats had transitional cell papilloma of the kidney. The increased incidence of neoplasms in the urinary bladder and kidney of rats
was also associated with an increase in renal calculi formation and hyperplasia of transitional cell epithelium. For the mouse study, sulfasalazine was tested at 675 (2025 mg/m2), 1350 (4050 mg/m2), and 2700 (8100 mg/m2) mg/kg/day.
The incidence of hepatocellular adenoma or carcinoma in male and female mice was significantly greater than the control at all doses tested.
[L39065]
Sulfasalazine did not show mutagenicity in the bacterial reverse mutation assay (Ames test) and in L51784 mouse lymphoma cell assay at the HGPRT gene. However, sulfasalazine showed an equivocal mutagenic response in the micronucleus assay of mouse
and rat bone marrow and mouse peripheral RBC and in the sister chromatid exchange, chromosomal aberration, and micronucleus assays in lymphocytes obtained from humans.
[L39065]
Impairment of male fertility was observed in reproductive studies performed in rats at a dose of 800 mg/kg/day (4800 mg/m2). Oligospermia and infertility have been described in men treated with sulfasalazine.
Withdrawal of the drug appears to reverse these effects.
[L39065]
There are no adequate and well-controlled studies of sulfasalazine in pregnant women. Reproduction studies have been performed in rats and rabbits at doses up to 6 times the human maintenance dose of 2 g/day based on body surface area and have revealed no evidence of impaired female fertility or harm to the fetus due to sulfasalazine. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
[L39065]
There have been case reports of neural tube defects (NTDs) in infants born to mothers who were exposed to sulfasalazine during pregnancy, but the role of sulfasalazine in these defects has not been established.
However, oral sulfasalazine inhibits the absorption and metabolism of folic acid which may interfere with folic acid supplementation (see Drug Interactions) and diminish the effect of periconceptional folic acid supplementation that has been shown to decrease the risk of NTDs.
[L39065]
A national survey evaluated the outcome of pregnancies associated with inflammatory bowel disease (IBD). In a group of 186 women treated with sulfasalazine alone or sulfasalazine and concomitant steroid therapy, the incidence of fetal morbidity and mortality was comparable to that for 245 untreated IBD pregnancies as well as to pregnancies in the general population. A study of 1,455 pregnancies associated with exposure to sulfonamides indicated that this group of drugs, including sulfasalazine, did
not appear to be associated with fetal malformation.
A review of the medical literature covering 1,155 pregnancies in women with ulcerative colitis suggested that the outcome was similar to that expected in the general population.
[L39065]
No clinical studies have been performed to evaluate the effect of sulfasalazine on the growth development and functional maturation of children whose mothers received the drug during pregnancy.
[L39065]
In female rats, two (4%) of the 337.5 mg/kg rats had transitional cell papilloma of the kidney. The increased incidence of neoplasms in the urinary bladder and kidney of rats
was also associated with an increase in renal calculi formation and hyperplasia of transitional cell epithelium. For the mouse study, sulfasalazine was tested at 675 (2025 mg/m2), 1350 (4050 mg/m2), and 2700 (8100 mg/m2) mg/kg/day.
The incidence of hepatocellular adenoma or carcinoma in male and female mice was significantly greater than the control at all doses tested.
[L39065]
Sulfasalazine did not show mutagenicity in the bacterial reverse mutation assay (Ames test) and in L51784 mouse lymphoma cell assay at the HGPRT gene. However, sulfasalazine showed an equivocal mutagenic response in the micronucleus assay of mouse
and rat bone marrow and mouse peripheral RBC and in the sister chromatid exchange, chromosomal aberration, and micronucleus assays in lymphocytes obtained from humans.
[L39065]
Impairment of male fertility was observed in reproductive studies performed in rats at a dose of 800 mg/kg/day (4800 mg/m2). Oligospermia and infertility have been described in men treated with sulfasalazine.
Withdrawal of the drug appears to reverse these effects.
[L39065]
There are no adequate and well-controlled studies of sulfasalazine in pregnant women. Reproduction studies have been performed in rats and rabbits at doses up to 6 times the human maintenance dose of 2 g/day based on body surface area and have revealed no evidence of impaired female fertility or harm to the fetus due to sulfasalazine. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
[L39065]
There have been case reports of neural tube defects (NTDs) in infants born to mothers who were exposed to sulfasalazine during pregnancy, but the role of sulfasalazine in these defects has not been established.
However, oral sulfasalazine inhibits the absorption and metabolism of folic acid which may interfere with folic acid supplementation (see Drug Interactions) and diminish the effect of periconceptional folic acid supplementation that has been shown to decrease the risk of NTDs.
[L39065]
A national survey evaluated the outcome of pregnancies associated with inflammatory bowel disease (IBD). In a group of 186 women treated with sulfasalazine alone or sulfasalazine and concomitant steroid therapy, the incidence of fetal morbidity and mortality was comparable to that for 245 untreated IBD pregnancies as well as to pregnancies in the general population. A study of 1,455 pregnancies associated with exposure to sulfonamides indicated that this group of drugs, including sulfasalazine, did
not appear to be associated with fetal malformation.
A review of the medical literature covering 1,155 pregnancies in women with ulcerative colitis suggested that the outcome was similar to that expected in the general population.
[L39065]
No clinical studies have been performed to evaluate the effect of sulfasalazine on the growth development and functional maturation of children whose mothers received the drug during pregnancy.
[L39065]
How it works
Mechanism of action
Although the exact mechanism of action of sulfasalazine is not fully understood, it is thought to be mediated through the inhibition of various inflammatory molecules.[L44478] Research have found that sulfasalazine and its metabolites, mesalazine and sulfapyridine, can inhibit leukotrienes and prostaglandins by blocking the cyclo-oxygenase and lipoxygenase pathway.[A255143] Specific enzymes that were investigated include phospholipase A2, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX2), and arachidonate 5-lipoxygenase.[A16801][A10316][A4391][A10319] Inhibitory activities on other non-arachidonic acid derivatives have also been observed, including PPAR gamma, NF-Kb, and IkappaB kinases alpha and beta.[A16799][A16797][A255577][A255138]
Pharmacodynamics
The mode of action of sulfasalazine or its metabolites, 5-aminosalicylic acid and sulfapyridine, is still under investigation but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and in vitro models, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver, and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of sulfasalazine, sulfapyridine, and 5-aminosalicylic acid have indicated that the major therapeutic action may reside in the 5-aminosalicylic acid moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown.[L39065]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Following oral administration of 1 g of sulfasalazine to 9 healthy males, less than 15% of a dose of sulfasalazine is absorbed as the parent drug. Detectable serum concentrations of sulfasalazine have been found in healthy subjects within 90 minutes after ingestion. Maximum concentrations of sulfasalazine occur between 3 and 12 hours post-ingestion, with the mean peak concentration (6 μg/mL) occurring at 6 hours.
[L39065]
[L39065]
Half-life
The observed plasma half-life for intravenous sulfasalazine is 7.6 ± 3.4 hours.
[L39065]
In fast acetylators, the mean plasma half-life of sulfapyridine is 10.4 hours while in slow acetylators, it is 14.8 hours.
[L39065]
Due to low plasma levels produced by
5-aminosalicylic acid after oral administration, reliable estimates of plasma half-life are not possible.
[L39065]
[L39065]
In fast acetylators, the mean plasma half-life of sulfapyridine is 10.4 hours while in slow acetylators, it is 14.8 hours.
[L39065]
Due to low plasma levels produced by
5-aminosalicylic acid after oral administration, reliable estimates of plasma half-life are not possible.
[L39065]
Protein binding
Sulfasalazine is highly bound to albumin (>99.3%) while sulfapyridine is only about 70% bound to albumin. Acetylsulfapyridine, the principal metabolite of sulfapyridine, is approximately 90% bound to plasma proteins.
[L39065]
[L39065]
Volume of distribution
Following intravenous injection, the calculated volume of distribution for sulfasalazine was 7.5 ± 1.6 L.
[L39065]
[L39065]
Metabolism
In the intestine, sulfasalazine is metabolized by intestinal bacteria to sulfapyridine and 5-aminosalicylic acid. Of the two species, sulfapyridine is relatively well absorbed from the intestine and highly metabolized, while 5-aminosalicylic acid is much less well absorbed.
[L39065]
Approximately 15% of a dose of sulfasalazine is absorbed as the parent drug and is metabolized to some extent in the liver to the same two species.
[L39065]
Sulfapyridine can also be metabolized to 5-hydroxysulfapyridine and N-acetyl-5-hydroxy sulfapyridine. 5-aminosalicylic acid is primarily metabolized in both the liver and intestine to N-acetyl-5 aminosalicylic acid via a non-acetylation phenotype-dependent route.
[L39065]
[L39065]
Approximately 15% of a dose of sulfasalazine is absorbed as the parent drug and is metabolized to some extent in the liver to the same two species.
[L39065]
Sulfapyridine can also be metabolized to 5-hydroxysulfapyridine and N-acetyl-5-hydroxy sulfapyridine. 5-aminosalicylic acid is primarily metabolized in both the liver and intestine to N-acetyl-5 aminosalicylic acid via a non-acetylation phenotype-dependent route.
[L39065]
Route of elimination
Absorbed sulfapyridine and 5-aminosalicylic acid and their metabolites are primarily eliminated in the urine either as free metabolites or as glucuronide conjugates. The majority of 5-ASA stays within the colonic lumen and is excreted as 5-aminosalicylic acid and acetyl-5-aminosalicylic acid in the feces.
[L39065]
[L39065]
Clearance
The calculated clearance of sulfasalazine following intravenous administration was 1 L/hr. Renal clearance was estimated to account for 37% of total clearance.
[L39065]
[L39065]
Drug targets(15)
Proteins and enzymes this drug interacts with in the body
Polyunsaturated fatty acid 5-lipoxygenase
ALOX5
inhibitor
Specific functionarachidonate 12(S)-lipoxygenase activity
Cellular location
Cytoplasm
General function & pharmacology
Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation .
PMID:19022417 PMID:21233389 PMID:22516296 PMID:23246375 PMID:24282679 PMID:24893149 PMID:31664810 PMID:8615788 PMID:8631361
Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) .
PMID:23246375
Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene .
PMID:31664810
Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses .
PMID:17114001 PMID:21206090 PMID:31664810 PMID:32404334 PMID:8615788
Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers .
PMID:31664810
In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 .
PMID:21200133
May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity).
Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)
PMID:19022417 PMID:21233389 PMID:22516296 PMID:23246375 PMID:24282679 PMID:24893149 PMID:31664810 PMID:8615788 PMID:8631361
Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) .
PMID:23246375
Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene .
PMID:31664810
Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses .
PMID:17114001 PMID:21206090 PMID:31664810 PMID:32404334 PMID:8615788
Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers .
PMID:31664810
In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 .
PMID:21200133
May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity).
Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity)
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)
Acetyl-CoA acetyltransferase, mitochondrial
ACAT1
inhibitor
Specific functionacetyl-CoA C-acetyltransferase activity
Cellular location
Mitochondrion
General function & pharmacology
This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA .
PMID:1715688 PMID:7728148 PMID:9744475
Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms .
PMID:1715688 PMID:7728148 PMID:9744475
The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA .
PMID:17371050
Thereby, it plays a major role in ketone body metabolism PMID:1715688 PMID:17371050 PMID:7728148 PMID:9744475
PMID:1715688 PMID:7728148 PMID:9744475
Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms .
PMID:1715688 PMID:7728148 PMID:9744475
The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA .
PMID:17371050
Thereby, it plays a major role in ketone body metabolism PMID:1715688 PMID:17371050 PMID:7728148 PMID:9744475
Phospholipase A2
PLA2G1B
antagonist
Specific functionbile acid binding
Cellular location
Secreted
General function & pharmacology
Secretory calcium-dependent phospholipase A2 that primarily targets dietary phospholipids in the intestinal tract .
PMID:10681567 PMID:1420353 PMID:17603006
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:10681567 PMID:1420353 PMID:17603006
May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation in the intestinal tract. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (By similarity). May act in an autocrine and paracrine manner .
PMID:25335547 PMID:7721806
Upon binding to the PLA2R1 receptor can regulate podocyte survival and glomerular homeostasis .
PMID:25335547
Has anti-helminth activity in a process regulated by gut microbiota.
Upon helminth infection of intestinal epithelia, directly affects phosphatidylethanolamine contents in the membrane of helminth larvae, likely controlling an array of phospholipid-mediated cellular processes such as membrane fusion and cell division while providing for better immune recognition, ultimately reducing larvae integrity and infectivity (By similarity)
PMID:10681567 PMID:1420353 PMID:17603006
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:10681567 PMID:1420353 PMID:17603006
May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation in the intestinal tract. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamines (By similarity). May act in an autocrine and paracrine manner .
PMID:25335547 PMID:7721806
Upon binding to the PLA2R1 receptor can regulate podocyte survival and glomerular homeostasis .
PMID:25335547
Has anti-helminth activity in a process regulated by gut microbiota.
Upon helminth infection of intestinal epithelia, directly affects phosphatidylethanolamine contents in the membrane of helminth larvae, likely controlling an array of phospholipid-mediated cellular processes such as membrane fusion and cell division while providing for better immune recognition, ultimately reducing larvae integrity and infectivity (By similarity)
Transporters(7)
Proteins that transport this drug across cell membranes
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells .
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
ATP-binding cassette sub-family C member 2
ABCC2
substrate
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
Proton-coupled folate transporter
SLC46A1
inhibitor
Specific functionfolic acid binding
Cellular location
Cell membrane
General function & pharmacology
Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:19762432 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:31792273 PMID:32893190 PMID:34619546
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:32893190
Functions at acidic pH via alternate outward- and inward-open conformation states .
PMID:32893190 PMID:34040256
Protonation of residues in the outward open state primes the protein for transport .
PMID:34040256
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate .
PMID:34040256
Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases .
PMID:18524888 PMID:19762432 PMID:22345511 PMID:25608532 PMID:28802835 PMID:29326243 PMID:34040256 PMID:34619546
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes .
PMID:19074442
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine .
PMID:17156779
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells .
PMID:32621820
Hence, participates in the trafficking of heme and increases intracellular iron content PMID:32621820
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:19762432 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:31792273 PMID:32893190 PMID:34619546
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:32893190
Functions at acidic pH via alternate outward- and inward-open conformation states .
PMID:32893190 PMID:34040256
Protonation of residues in the outward open state primes the protein for transport .
PMID:34040256
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate .
PMID:34040256
Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases .
PMID:18524888 PMID:19762432 PMID:22345511 PMID:25608532 PMID:28802835 PMID:29326243 PMID:34040256 PMID:34619546
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes .
PMID:19074442
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine .
PMID:17156779
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells .
PMID:32621820
Hence, participates in the trafficking of heme and increases intracellular iron content PMID:32621820
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
Solute carrier organic anion transporter family member 1B3
SLCO1B3
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate 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
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
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 pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
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
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate 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
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
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 pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
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
Solute carrier organic anion transporter family member 2B1
SLCO2B1
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions .
PMID:10873595 PMID:11159893 PMID:11932330 PMID:12724351 PMID:14610227 PMID:16908597 PMID:18501590 PMID:20507927 PMID:22201122 PMID:23531488 PMID:25132355 PMID:26383540 PMID:27576593 PMID:28408210 PMID:29871943 PMID:34628357
Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) .
PMID:11932330 PMID:12409283
Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver .
PMID:11159893
Mediates the intestinal uptake of sulfated steroids .
PMID:12724351 PMID:28408210
Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain .
PMID:16908597 PMID:25132355
Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC .
PMID:35714613
Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition .
PMID:26383540
Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). 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:14610227 PMID:19129463 PMID:22201122
The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound .
PMID:19129463 PMID:20507927 PMID:26277985
Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions .
PMID:19129463
Cytoplasmic glutamate may also act as counteranion in the placenta .
PMID:26277985
An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) PMID:20507927
PMID:10873595 PMID:11159893 PMID:11932330 PMID:12724351 PMID:14610227 PMID:16908597 PMID:18501590 PMID:20507927 PMID:22201122 PMID:23531488 PMID:25132355 PMID:26383540 PMID:27576593 PMID:28408210 PMID:29871943 PMID:34628357
Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) .
PMID:11932330 PMID:12409283
Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver .
PMID:11159893
Mediates the intestinal uptake of sulfated steroids .
PMID:12724351 PMID:28408210
Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain .
PMID:16908597 PMID:25132355
Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC .
PMID:35714613
Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition .
PMID:26383540
Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). 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:14610227 PMID:19129463 PMID:22201122
The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound .
PMID:19129463 PMID:20507927 PMID:26277985
Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions .
PMID:19129463
Cytoplasmic glutamate may also act as counteranion in the placenta .
PMID:26277985
An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) PMID:20507927
Hepatic sodium/bile acid cotransporter
SLC10A1
inhibitor
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
Carriers(1)
Proteins that carry this drug through the body
Albumin
ALB
binder
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
Scientific references(14)
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Pharmacological and biochemical actions of sulphasalazine.
Drugs
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Weber C.K., Liptay S., Wirth T., Adler G., Schmid R.M.
Suppression of NF-κB activity by sulfasalazine is mediated by direct inhibition of IκB kinases α and β.
Gastroenterology
2000119(5):1209-1218. doi: 10.1053/gast.2000.19458
Generini S., Fiori G., Matucci Cerinic M.
The pathogenesis of inflammatory muscle diseases:.
Autoimmunity Reviews
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Allgayer H.
Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease.
Alimentary Pharmacology & Therapeutics
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Pruzanski W., Stefanski E., Vadas P., Ramamurthy N.S.
Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine.
Biochemical Pharmacology
199753(12):1901-1907. doi: 10.1016/s0006-2952(97)00137-8
Nielsen O.H., Bukhave K., Elmgreen J., Ahnfelt-Ronne I.
Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid.
Digestive Diseases and Sciences
198732(6):577-582. doi: 10.1007/bf01296156
Rousseaux C., Lefebvre B., Dubuquoy L., Lefebvre P., Romano O., Auwerx J., Metzger D., Wahli W., Desvergne B., Naccari G.C., Chavatte P., Farce A., Bulois P., Cortot A., Colombel J.F., Desreumaux P.
Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ.
The Journal of Experimental Medicine
2005201(8):1205-1215. doi: 10.1084/jem.20041948
Cevallos S.A., Lee J.Y., Velazquez E.M., Foegeding N.J., Shelton C.D., Tiffany C.R., Parry B.H., Stull-Lane A.R., Olsan E.E., Savage H.P., Nguyen H., Ghanaat S.S., Byndloss A.J., Agu I.O., Tsolis R.M., Byndloss M.X., Baumler A.J.
5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-gamma Signaling in the Intestinal Epithelium.
mBio
2021 Jan 1912(1):e03227-20. doi: 10.1128/mBio.03227-20
Wahl C., Liptay S., Adler G., Schmid R.M.
Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B.
Journal Clinical Invest
1998 Mar 1101(5):1163-74. doi: 10.1172/JCI992
Rains C.P., Noble S., Faulds D.
Sulfasalazine.
A review of its pharmacological properties and therapeutic efficacy in the treatment of rheumatoid arthritis
Drugs. 1995 Jul50(1):137-56. doi: 10.2165/00003495-199550010-00009
Peppercorn M.A.
Sulfasalazine.
Pharmacology, clinical use, toxicity, and related new drug development
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Lim W.C., Wang Y., MacDonald J.K., Hanauer S.
Aminosalicylates for induction of remission or response in Crohn's disease.
Cochrane Database of Systematic Reviews
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Rapid recommendations.
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Budesonide – Oral Galenic Formulations for Crohn Disease.
Annals of Clinical Gastroenterology and Hepatology
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ATC classification(2 codes)
ATC G01AE10
ATC A07EC01
Affected organisms(1)
Humans and other mammals
International brands(29)
Experimental properties(4)
Commercial products(60)
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)
Sulfasalazine
Additional database identifiers
Drugs Product Database (DPD)
8138
ChemSpider
10605946
BindingDB
50103596
PDB
SAS
ZINC
ZINC000003831490
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: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:93
GenAtlas
ACAT1
GeneCards
ACAT1
GenBank Gene Database
D90228
GenBank Protein Database
219918
Guide to Pharmacology
2435
UniProt Accession
THIL_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9030
GeneCards
PLA2G1B
GenBank Gene Database
M21054
GenBank Protein Database
190013
Guide to Pharmacology
1416
UniProt Accession
PA21B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:5960
GenAtlas
IKBKB
GeneCards
IKBKB
GenBank Gene Database
AF029684
GenBank Protein Database
2599558
Guide to Pharmacology
2039
UniProt Accession
IKKB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9954
GeneCards
REL
UniProt Accession
REL_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9956
GeneCards
RELB
UniProt Accession
RELB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9955
GeneCards
RELA
Guide to Pharmacology
3280
UniProt Accession
TF65_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:11059
GenAtlas
SLC7A11
GeneCards
SLC7A11
GenBank Gene Database
AB026891
GenBank Protein Database
5668545
Guide to Pharmacology
902
UniProt Accession
XCT_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7794
GenAtlas
NFKB1
GeneCards
NFKB1
GenBank Gene Database
M55643
GenBank Protein Database
189180
UniProt Accession
NFKB1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7795
GenAtlas
NFKB2
GeneCards
NFKB2
GenBank Gene Database
X61498
UniProt Accession
NFKB2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1974
GeneCards
CHUK
Guide to Pharmacology
1989
UniProt Accession
IKKA_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:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_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:30521
GenAtlas
SLC46A1
GeneCards
SLC46A1
GenBank Gene Database
AK054669
GenBank Protein Database
16549261
Guide to Pharmacology
1213
UniProt Accession
PCFT_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:10961
GeneCards
SLCO1B3
GenBank Gene Database
AJ251506
GenBank Protein Database
9187497
Guide to Pharmacology
1221
UniProt Accession
SO1B3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10962
GenAtlas
SLCO2B1
GeneCards
SLCO2B1
GenBank Gene Database
AB026256
GenBank Protein Database
5006263
Guide to Pharmacology
1224
UniProt Accession
SO2B1_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
International reference pricing
11 formulations
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
From $0.22/tablet
To $2.14/g
Pms-Sulfasalazine 500 mg Tablet
$0.22/tablet
Sulfasalazine 500 mg tablet
$0.25/tablet
Sulfazine 500 mg tablet
$0.25/tablet
Salazopyrin 500 mg Tablet
$0.28/tablet
Pms-Sulfasalazine 500 mg Enteric-Coated Tablet
$0.34/tablet
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
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 26 days ago(8 Mar 2026)