Salsalate

Identification

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Name
Salsalate
Accession Number
DB01399
Type
Small Molecule
Groups
Approved
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
  • Disalicylic acid
  • Disalicylsäure
  • O-Salicylcylsalicylsäure
  • o-Salicylsalicylic acid
  • Salicylic acid bimolecular ester
  • Salicyloxysalicylic acid
  • Salicyloylsalicylic acid
  • Salicylsalicylic acid
  • Salsalate
  • Salsalato
  • Salsalatum
  • Sasapyrin
  • Sasapyrine
  • Sasapyrinum
External IDs
NSC-49171
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DisalcidTablet750 mg/1OralAvion Pharmaceuticals, Llc2014-09-182016-05-31Us
DisalcidTablet500 mg/1OralAvion Pharmaceuticals, Llc2014-09-182016-05-31Us
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
SalsalateTablet500 mg/1OralMajor1998-08-032013-11-30Us
SalsalateTablet750 mg/1OralRebel Distributors1995-04-01Not applicableUs
SalsalateTablet500 mg/1OralAv Pak2014-11-182017-05-01Us65162 0512 10 nlmimage10 151c8ae4
SalsalateTablet500 mg/1OralPhysicians Total Care, Inc.2004-01-232013-01-15Us
Additional Data Available
  • Application Number
    Application Number

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  • Product Code
    Product Code

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Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DisalcidSalsalate (750 mg/1)TabletOralAvion Pharmaceuticals, Llc2014-09-182016-05-31Us
DisalcidSalsalate (500 mg/1)TabletOralAvion Pharmaceuticals, Llc2014-09-182016-05-31Us
SalsalateSalsalate (750 mg/1)TabletOralAv Pak2015-02-182017-05-01Us
SalsalateSalsalate (500 mg/1)TabletOralPhysicians Total Care, Inc.2004-01-232013-01-15Us
SalsalateSalsalate (500 mg/1)TabletOralEci Pharmaceuticals Llc2014-10-01Not applicableUs
SalsalateSalsalate (750 mg/1)TabletOralCarilion Materials Management2010-09-24Not applicableUs65162 0513 50 nlmimage10 210e90d4
SalsalateSalsalate (500 mg/1)TabletOralAv Pak2014-11-182017-05-01Us65162 0512 10 nlmimage10 151c8ae4
SalsalateSalsalate (500 mg/1)TabletOralMethod Pharmaceuticals2016-11-23Not applicableUs
SalsalateSalsalate (750 mg/1)TabletOralAcella Pharmaceuticals, LLC2014-03-31Not applicableUs
SalsalateSalsalate (750 mg/1)Tablet, film coatedOralMarlex Pharmaceuticals Inc2007-04-01Not applicableUs
Categories
UNII
V9MO595C9I
CAS number
552-94-3
Weight
Average: 258.2262
Monoisotopic: 258.05282343
Chemical Formula
C14H10O5
InChI Key
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

Pharmacology

Indication

For relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders.

Pharmacodynamics

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.

Mechanism of action

The 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.

TargetActionsOrganism
AProstaglandin G/H synthase 2
inhibitor
Humans
AProstaglandin G/H synthase 1
inhibitor
Humans
Additional Data Available
Adverse Effects

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Additional Data Available
Contraindications

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Additional Data Available
Blackbox Warnings

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Absorption

Salsalate 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 distribution
Not Available
Protein binding

Salicylate: 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 elimination
Not Available
Half life

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.

Clearance
Not Available
Toxicity

Death 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
PathwayCategory
Salsalate Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of gastrointestinal bleeding can be increased when Salsalate is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of gastrointestinal bleeding can be increased when Salsalate is combined with (S)-Warfarin.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Salsalate is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
1-benzylimidazoleThe risk or severity of hypertension can be increased when Salsalate is combined with 1-benzylimidazole.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of hypertension can be increased when Salsalate is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of hypertension can be increased when Salsalate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of hypertension can be increased when Salsalate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of gastrointestinal bleeding can be increased when Salsalate is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of hypertension can be increased when Salsalate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of hypertension can be increased when Salsalate is combined with 5-methoxy-N,N-dimethyltryptamine.
Additional Data Available
  • Extended Description
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  • Severity
    Severity

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  • Evidence Level
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Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015471
KEGG Drug
D00428
PubChem Compound
5161
PubChem Substance
46506882
ChemSpider
4977
BindingDB
85244
ChEBI
9014
ChEMBL
CHEMBL154111
Therapeutic Targets Database
DAP000734
PharmGKB
PA164745462
Wikipedia
Salsalate
ATC Codes
N02BA06 — Salsalate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentProgressive Supranuclear Palsy (PSP)1
1CompletedBasic ScienceAssessment of Mechanistic Blood Biomarkers in Healthy Humans1
1CompletedBasic ScienceDiabetes Risk1
1CompletedBasic ScienceInsulin Resistance1
1Not Yet RecruitingPreventionHyperglycemias / Perioperative/Postoperative Complications / Type 2 Diabetes Mellitus1
1RecruitingTreatmentAlzheimer's Disease (AD)1
1TerminatedBasic SciencePolycystic Ovaries Syndrome1
1, 2CompletedOtherInsulin Resistance1
2Active Not RecruitingTreatmentDiastolic Dysfunction / Endothelial Dysfunction / Vascular Stiffness1
2Active Not RecruitingTreatmentObese / Pre-Diabetic1
2CompletedPreventionBMI >30 kg/m21
2CompletedTreatmentEndothelial Dysfunction / Human Immunodeficiency Virus (HIV) / Inflammatory Reaction / Insulin Resistance1
2CompletedTreatmentPeripheral Neuropathy / Type 1 Insulin-Dependent Diabetes Mellitus1
2RecruitingBasic SciencePolycystic Ovaries Syndrome1
2TerminatedTreatmentAnemias1
2, 3CompletedBasic ScienceMetabolic Syndromes1
2, 3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Inflammatory Reaction / Insulin Resistance / Noninsulin-dependent Diabetes Mellitus1
2, 3CompletedPreventionBMI >27 kg/m2 / Coronary Artery Disease1
2, 3CompletedTreatmentAtherosclerosis1
2, 3CompletedTreatmentType 2 Diabetes Mellitus2
2, 3RecruitingTreatmentPeripheral Neuropathy / Type 1 Insulin-Dependent Diabetes Mellitus1
4Active Not RecruitingTreatmentNon Alcoholic Fatty Liver / Osteoarthritis (OA)1
4CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
Not AvailableCompletedNot AvailableInsulin Resistant / Pre Diabetes1
Not AvailableCompletedPreventionDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / Pre-Diabetic1
Not AvailableCompletedTreatmentInsulin Resistance / Schizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • 3M Health Care
  • Advanced Pharmaceutical Services Inc.
  • Amarin Pharmaceuticals
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Boca Pharmacal
  • Caraco Pharmaceutical Labs
  • Comprehensive Consultant Services Inc.
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Golden State Medical Supply Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Professional Co.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Schwarz Pharma Inc.
  • Southwood Pharmaceuticals
  • Sunrise Pharmaceutical Inc.
  • Superior Pharmeceuticals
  • United Research Laboratories Inc.
  • Va Cmop Dallas
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)147 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (7.76 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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).
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Depsides and depsidones
Sub Class
Not Available
Direct Parent
Depsides and depsidones
Alternative Parents
o-Hydroxybenzoic acid esters / Salicylic acid and derivatives / Phenol esters / Benzoic acids / Phenoxy compounds / Benzoyl derivatives / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Dicarboxylic acids and derivatives / Vinylogous acids
show 5 more
Substituents
Depside backbone / O-hydroxybenzoic acid ester / Benzoate ester / Salicylic acid or derivatives / Phenol ester / Benzoic acid or derivatives / Benzoic acid / Phenoxy compound / Benzoyl / 1-hydroxy-4-unsubstituted benzenoid
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
phenols, salicylates, benzoate ester, benzoic acids (CHEBI:9014)

Targets

Kind
Protein
Organism
Humans
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...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
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
Humans
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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
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]

Drug created on July 08, 2007 11:05 / Updated on June 04, 2019 05:16