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Identification
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
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Synonyms
  • salicylsalicylic acid
  • Salsalatum [inn-latin]
  • Sasapyrine
Brand names
  • Disalcid
Brand name mixtures Not Available
Categories Not Available
CAS number 552-94-3
Weight Average: 258.2262
Monoisotopic: 258.052823430
Chemical Formula C14H10O5
InChI Key InChIKey=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)
Plain Text
IUPAC Name
2-[(2-hydroxyphenyl)carbonyloxy]benzoic acid
SMILES
OC(=O)C1=C(OC(=O)C2=C(O)C=CC=C2)C=CC=C1
Plain Text
Mass Spec show (7.8 KB)
Taxonomy
Kingdom Not Available
Classes
  • Benzoates
  • Salicylates and Derivatives
  • Phenylacetates
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Salicylates and Derivatives
  • Phenols and Derivatives
  • Phenylacetates
  • Ethers
  • Benzene and Derivatives
  • Aromatic compounds
  • Anisoles
  • Benzoyl Derivatives
  • Phenyl Esters
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.
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 Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Salsalate powder 16.8 USD g
Salsalate 750 mg tablet 0.55 USD tablet
Salflex-750 tablet 0.5 USD tablet
Salflex-500 tablet 0.37 USD tablet
Salsalate 500 mg tablet 0.26 USD tablet
Patents Not Available
Properties
State solid
Melting point 147 oC
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 2.46e-01 g/l ALOGPS
logP 3.44 ALOGPS
logP 3.64 ChemAxon Molconvert
logS -3.02 ALOGPS
pKa 9.67 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 83.83 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 67.10 ChemAxon Molconvert
polarizability 24.92 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00428 Link_out
PubChem Compound 5161 Link_out
PubChem Substance 46506882 Link_out
ChemSpider 4977 Link_out
Therapeutic Targets Database DAP000734 Link_out
PharmGKB PA451303 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/salsalate.htm Link_out
Drugs.com http://www.drugs.com/cdi/salsalate.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dis1142.shtml Link_out
ATC Codes
  • N02BA06
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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

2. Prostaglandin G/H synthase 1

Pharmacological action: yes
Actions: inhibitor

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Stevenson DD: Aspirin and NSAID sensitivity. Immunol Allergy Clin North Am. 2004 Aug;24(3):491-505, vii. Pubmed
  2. 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
    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
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on July 08, 2007 11:05 / Updated on November 23, 2010 12:57

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.