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Identification
NameSalsalate
Accession NumberDB01399
TypeSmall Molecule
GroupsApproved
Description

Salsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate’s mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo. Salsalate is readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body. The parent compound has an elimination half-life of about 1 hour. Salicylic acid (the active metabolite) biotransformation is saturated at anti-inflammatory doses of salsalate. Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours.

Structure
Thumb
Synonyms
2-Carboxyphenyl salicylate
Disalcid
Disalicylic acid
Disalicylsaeure
O-Salicylcylsalicylsaeure
O-Salicylsalicylic acid
Salicylic acid bimolecular ester
Salicyloxysalicylic acid
Salicyloylsalicylic acid
salicylsalicylic acid
Salsalato
Salsalatum
Sasapyrin
Sasapyrine
Sasapyrinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Disalcid - Tab 500mgtablet500 mgoral3 M Pharmaceuticals, A Division Of 3 M Canada Company1996-10-012002-07-09Canada
Disalcid - Tab 750mgtablet750 mgoral3 M Pharmaceuticals, A Division Of 3 M Canada Company1996-06-012002-07-09Canada
Disalcid Tab 500mgtablet500 mgoral3 M Pharmaceuticals, A Division Of 3 M Canada Company1993-12-311999-10-27Canada
Disalcid Tab 750mgtablet750 mgoral3 M Pharmaceuticals, A Division Of 3 M Canada Company1993-12-311999-10-27Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Disalcidtablet750 mg/1oralAvion Pharmaceuticals, Llc2014-09-18Not applicableUs
Disalcidtablet500 mg/1oralAvion Pharmaceuticals, Llc2014-09-18Not applicableUs
Salsalatetablet750 mg/1oralbryant ranch prepack1995-04-01Not applicableUs
Salsalatetablet750 mg/1oralLibertas Pharma, Inc.2011-05-22Not applicableUs
Salsalatetablet750 mg/1oralAv Pak2014-11-18Not applicableUs
Salsalatetablet500 mg/1oralAv Pak2014-11-18Not applicableUs
Salsalatetablet750 mg/1oralAcella Pharmaceuticals, LLC2011-05-16Not applicableUs
Salsalatetablet500 mg/1oralMajor Pharmaceuticals1998-08-03Not applicableUs
Salsalatetablet500 mg/1oralAmneal Pharmaceuticals2010-09-24Not applicableUs
Salsalatetablet750 mg/1oralClinical Solutions Wholesale2010-09-24Not applicableUs
Salsalatetablet500 mg/1oralLibertas Pharma, Inc.2011-05-22Not applicableUs
Salsalatetablet750 mg/1oralLake Erie Medical & Surgical Supply DBA Quality Care Products LLC2010-09-24Not applicableUs
Salsalatetablet500 mg/1oralAcella Pharmaceuticals, LLC2011-05-16Not applicableUs
Salsalatetablet, film coated750 mg/1oralBoca Pharmacal, Inc.2012-01-162015-12-29Us
Salsalatetablet500 mg/1oralClinical Solutions Wholesale2010-09-24Not applicableUs
Salsalatetablet750 mg/1oralECI Pharmaceuticals, LLC2014-10-01Not applicableUs
Salsalatetablet750 mg/1oralAphena Pharma Solutions Tennessee, Inc.2011-05-22Not applicableUs
Salsalatetablet750 mg/1oralRebel Distributors Corp1995-04-01Not applicableUs
Salsalatetablet, film coated500 mg/1oralBoca Pharmacal, Inc.2012-01-162015-12-29Us
Salsalatetablet750 mg/1oralPd Rx Pharmaceuticals, Inc.2011-05-16Not applicableUs
Salsalatetablet750 mg/1oralCaraco Pharmaceutical Laboratories, Ltd.1995-04-01Not applicableUs
Salsalatetablet500 mg/1oralECI Pharmaceuticals, LLC2014-10-01Not applicableUs
Salsalatetablet, film coated750 mg/1oralNationwide Laboratories, LLC2011-08-19Not applicableUs
Salsalatetablet500 mg/1oralCaraco Pharmaceutical Laboratories, Ltd.1995-04-01Not applicableUs
Salsalatetablet, film coated750 mg/1oral3 T Federal Solutions Llc2012-01-16Not applicableUs
Salsalatetablet, film coated500 mg/1oralNationwide Laboratories, LLC2011-08-19Not applicableUs
Salsalatetablet, film coated750 mg/1oralMarlex Pharmaceuticals Inc2007-04-01Not applicableUs
Salsalatetablet750 mg/1oralCarilion Materials Management2010-09-24Not applicableUs
Salsalatetablet750 mg/1oralPd Rx Pharmaceuticals, Inc.2010-09-24Not applicableUs
Salsalatetablet, film coated500 mg/1oral3 T Federal Solutions Llc2012-01-16Not applicableUs
Salsalatetablet750 mg/1oralAv Kare, Inc.2013-05-172016-02-03Us
Salsalatetablet, film coated500 mg/1oralMarlex Pharmaceuticals Inc2007-04-01Not applicableUs
Salsalatetablet500 mg/1oralCarilion Materials Management2010-09-24Not applicableUs
Salsalatetablet500 mg/1oralPd Rx Pharmaceuticals, Inc.2010-09-24Not applicableUs
Salsalatetablet750 mg/1oralAv Pak2015-02-18Not applicableUs
Salsalatetablet750 mg/1oralA S Medication Solutions Llc2010-09-24Not applicableUs
Salsalatetablet500 mg/1oralAv Pak2015-02-18Not applicableUs
Salsalatetablet500 mg/1oralAv Kare, Inc.2013-05-172016-02-03Us
Salsalatetablet750 mg/1oralMajor Pharmaceuticals2004-01-29Not applicableUs
Salsalatetablet750 mg/1oralAmneal Pharmaceuticals2010-09-24Not applicableUs
Salsalate Rxtablet, film coated750 mg/1oralAnda Pharm Llc2015-01-01Not applicableUs
Salsalate Rxtablet, film coated500 mg/1oralAnda Pharm Llc2015-01-01Not applicableUs
International Brands
NameCompany
DisalcidNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIV9MO595C9I
CAS number552-94-3
WeightAverage: 258.2262
Monoisotopic: 258.05282343
Chemical FormulaC14H10O5
InChI KeyInChIKey=WVYADZUPLLSGPU-UHFFFAOYSA-N
InChI
InChI=1S/C14H10O5/c15-11-7-3-1-5-9(11)14(18)19-12-8-4-2-6-10(12)13(16)17/h1-8,15H,(H,16,17)
IUPAC Name
2-(2-hydroxybenzoyloxy)benzoic acid
SMILES
OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as depsides and depsidones. These are polycyclic compounds that is either a polyphenolic compound composed of two or more monocyclic aromatic units linked by an ester bond (depside), or a compound containing the depsidone structure (depsidone).
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassDepsides and depsidones
Sub ClassNot Available
Direct ParentDepsides and depsidones
Alternative Parents
Substituents
  • Depside backbone
  • Salicylic acid or derivatives
  • Phenol ester
  • Benzoate ester
  • Benzoic acid
  • Benzoic acid or derivatives
  • Benzoyl
  • Phenol
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Vinylogous acid
  • Carboxylic acid ester
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders.
PharmacodynamicsSalsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo.
Mechanism of actionThe mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 (COX-1) and COX-2, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salsalate) is a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, salsalate does not inhibit platelet aggregation.
Related Articles
AbsorptionSalsalate is insoluble in acid gastric fluids (< 0.1 mg/ml at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged. The amount of salicylic acid available from salsalate is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salsalate/5 g aspirin). Food slows the absorption of all salicylates including salsalate.
Volume of distributionNot Available
Protein bindingSalicylate: 90-95% bound at plasma salicylate concentrations <100 mcg/mL; 70-85% bound at concentrations of 100-400 mcg/mL; 25-60% bound at concentrations >400 mcg/mL.
Metabolism

Salsalate is readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body.

Route of eliminationNot Available
Half lifeThe parent compound has an elimination half-life of about 1 hour. Salicylic acid (the active metabolite) biotransformation is saturated at anti-inflammatory doses of salsalate. Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours.
ClearanceNot Available
ToxicityDeath has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Salsalate Action PathwayDrug actionSMP00707
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9161
Blood Brain Barrier+0.8946
Caco-2 permeable+0.5186
P-glycoprotein substrateNon-substrate0.6391
P-glycoprotein inhibitor INon-inhibitor0.8819
P-glycoprotein inhibitor IINon-inhibitor0.9074
Renal organic cation transporterNon-inhibitor0.8788
CYP450 2C9 substrateNon-substrate0.7946
CYP450 2D6 substrateNon-substrate0.9353
CYP450 3A4 substrateNon-substrate0.7281
CYP450 1A2 substrateNon-inhibitor0.7887
CYP450 2C9 inhibitorNon-inhibitor0.5411
CYP450 2D6 inhibitorNon-inhibitor0.9409
CYP450 2C19 inhibitorNon-inhibitor0.8028
CYP450 3A4 inhibitorNon-inhibitor0.9568
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8116
Ames testNon AMES toxic0.9731
CarcinogenicityNon-carcinogens0.8579
BiodegradationReady biodegradable0.5723
Rat acute toxicity2.4607 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9607
hERG inhibition (predictor II)Non-inhibitor0.9403
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral500 mg
Tabletoral750 mg
Tabletoral500 mg/1
Tabletoral750 mg/1
Tablet, film coatedoral500 mg/1
Tablet, film coatedoral750 mg/1
Prices
Unit descriptionCostUnit
Salsalate powder16.8USD g
Salsalate 750 mg tablet0.55USD tablet
Salflex-750 tablet0.5USD tablet
Salflex-500 tablet0.37USD tablet
Salsalate 500 mg tablet0.26USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point147 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.246 mg/mLALOGPS
logP3.44ALOGPS
logP3.64ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)3.4ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area83.83 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity67.1 m3·mol-1ChemAxon
Polarizability24.92 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.76 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesN02BA06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabSalsalate may increase the anticoagulant activities of Abciximab.
AcenocoumarolSalsalate may increase the anticoagulant activities of Acenocoumarol.
AcetazolamideThe risk or severity of adverse effects can be increased when Salsalate is combined with Acetazolamide.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Salsalate.
AlteplaseThe risk or severity of adverse effects can be increased when Salsalate is combined with Alteplase.
Ammonium chlorideThe serum concentration of Salsalate can be increased when it is combined with Ammonium chloride.
AnistreplaseThe risk or severity of adverse effects can be increased when Salsalate is combined with Anistreplase.
Citric AcidSalsalate may increase the anticoagulant activities of Citric Acid.
DalteparinSalsalate may increase the anticoagulant activities of Dalteparin.
DesmopressinThe risk or severity of adverse effects can be increased when Desmopressin is combined with Salsalate.
DexketoprofenThe risk or severity of adverse effects can be increased when Salsalate is combined with Dexketoprofen.
DiclofenamideThe risk or severity of adverse effects can be increased when Salsalate is combined with Diclofenamide.
DicoumarolSalsalate may increase the anticoagulant activities of Dicoumarol.
Edetic AcidSalsalate may increase the anticoagulant activities of Edetic Acid.
EnoxaparinSalsalate may increase the anticoagulant activities of Enoxaparin.
EthoxzolamideThe risk or severity of adverse effects can be increased when Salsalate is combined with Ethoxzolamide.
Ethyl biscoumacetateSalsalate may increase the anticoagulant activities of Ethyl biscoumacetate.
FludrocortisoneThe risk or severity of adverse effects can be increased when Salsalate is combined with Fludrocortisone.
Fondaparinux sodiumSalsalate may increase the anticoagulant activities of Fondaparinux sodium.
Ginkgo bilobaGinkgo biloba may increase the anticoagulant activities of Salsalate.
HeparinSalsalate may increase the anticoagulant activities of Heparin.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Salsalate.
Insulin HumanSalsalate may increase the hypoglycemic activities of Insulin Regular.
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Salsalate.
PerindoprilSalsalate may decrease the antihypertensive activities of Perindopril.
PhenindioneSalsalate may increase the anticoagulant activities of Phenindione.
PhenprocoumonSalsalate may increase the anticoagulant activities of Phenprocoumon.
PralatrexateThe serum concentration of Pralatrexate can be increased when it is combined with Salsalate.
ProbenecidThe therapeutic efficacy of Probenecid can be decreased when used in combination with Salsalate.
ReteplaseThe risk or severity of adverse effects can be increased when Salsalate is combined with Reteplase.
RidogrelThe risk or severity of adverse effects can be increased when Salsalate is combined with Ridogrel.
StreptokinaseThe risk or severity of adverse effects can be increased when Salsalate is combined with Streptokinase.
SulodexideSalsalate may increase the anticoagulant activities of Sulodexide.
TenecteplaseThe risk or severity of adverse effects can be increased when Salsalate is combined with Tenecteplase.
TorasemideSalsalate may decrease the diuretic activities of Torasemide.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Salsalate.
UrokinaseThe risk or severity of adverse effects can be increased when Salsalate is combined with Urokinase.
Valproic AcidThe serum concentration of Valproic Acid can be increased when it is combined with Salsalate.
WarfarinSalsalate may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Stichtenoth DO, Zeidler H, Frolich JC: [New non-steroidal anti-rheumatic drugs: selective inhibitors of inducible cyclooxygenase]. Med Klin (Munich). 1998 Jul 15;93(7):407-15. [PubMed:9711054 ]
  2. Schaefer MG, Plowman BK, Morreale AP, Egan M: Interaction of rofecoxib and celecoxib with warfarin. Am J Health Syst Pharm. 2003 Jul 1;60(13):1319-23. [PubMed:12901032 ]
  3. Motsko SP, Rascati KL, Busti AJ, Wilson JP, Barner JC, Lawson KA, Worchel J: Temporal relationship between use of NSAIDs, including selective COX-2 inhibitors, and cardiovascular risk. Drug Saf. 2006;29(7):621-32. [PubMed:16808554 ]
  4. Josephs MD, Cheng G, Ksontini R, Moldawer LL, Hocking MP: Products of cyclooxygenase-2 catalysis regulate postoperative bowel motility. J Surg Res. 1999 Sep;86(1):50-4. [PubMed:10452868 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. 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 gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Stevenson DD: Aspirin and NSAID sensitivity. Immunol Allergy Clin North Am. 2004 Aug;24(3):491-505, vii. [PubMed:15242723 ]
  2. Schmidt A, Hescheler J, Offermanns S, Spicher K, Hinsch KD, Klinz FJ, Codina J, Birnbaumer L, Gausepohl H, Frank R, et al.: Involvement of pertussis toxin-sensitive G-proteins in the hormonal inhibition of dihydropyridine-sensitive Ca2+ currents in an insulin-secreting cell line (RINm5F). J Biol Chem. 1991 Sep 25;266(27):18025-33. [PubMed:1680855 ]
  3. Josephs MD, Cheng G, Ksontini R, Moldawer LL, Hocking MP: Products of cyclooxygenase-2 catalysis regulate postoperative bowel motility. J Surg Res. 1999 Sep;86(1):50-4. [PubMed:10452868 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Comments
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Drug created on July 08, 2007 11:05 / Updated on September 16, 2013 17:14