Sulindac

Sulindac
Systematic (IUPAC) name
{(1Z)-5-fluoro-2-methyl-1-[4-(methylsulfinyl)benzylidene]-1H-indene-3-yl}acetic acid
Clinical data
Trade names Clinoril
AHFS/Drugs.com monograph
MedlinePlus a681037
  • AU: C
  • US: C (Risk not ruled out)
Oral
Pharmacokinetic data
Bioavailability Approximately 90% (Oral)
Metabolism ?
Half-life 7.8 hours, metabolites up to 16.4 hours
Excretion Renal (50%) and fecal (25%)
Identifiers
38194-50-2 Yes
M01AB02
PubChem CID 1548887
DrugBank DB00605 Yes
ChemSpider 1265915 Yes
UNII 184SNS8VUH Yes
KEGG D00120 Yes
ChEBI CHEBI:9352 Yes
ChEMBL CHEMBL15770 
PDB ligand ID SUZ (PDBe, RCSB PDB)
Chemical data
Formula C20H17FO3S
356.412 g/mol
Physical data
Melting point 182 to 185 °C (360 to 365 °F) (decomp.)
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Sulindac is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the UK & U.S. by Merck as Clinoril.

Uses

Like other NSAIDs, it is useful in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIDs except for drugs of the COX-2 inhibitor class . The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Its usual dosage is 150-200 milligrams twice per day, with food. It should not be used by persons with a history of major allergic reactions (urticaria or anaphylaxis) to aspirin or other NSAIDs, and should be used with caution by persons having pre-existing peptic ulcer disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas However it is less likely to cause kidney damage than other NSAIDs.

Sulindac seems to have a property, independent of COX-inhibition, of reducing the growth of polyps and precancerous lesions in the colon, especially in association with familial adenomatous polyposis, and may have other anti-cancer properties.[1][2]

Sulindac is an effective tocolytic and may be used in the treatment of preterm labor. In common with other NSAIDs, sulindac is currently being investigated for its role in the treatment of Alzheimer's disease.

Since it was found that the sulfoxide functional group can be reduced by methionine sulfoxide reductase A (MsrA), a possible anti-oxidative capability is being discussed.

Litigation

In September 2010 a federal jury in New Hampshire awarded $21 million to Karen Bartlett, a woman who developed Stevens–Johnson syndrome/Toxic epidermal necrolysis as a result of taking a generic brand of sulindac manufactured by Mutual Pharmaceuticals for her shoulder pain. Ms. Bartlett suffered severe injuries including the loss of over 60% of her surface skin and permanent near-blindness. The case had been appealed to the United States Supreme Court, where the main issue was whether federal law preempts Ms. Bartlett's claim.[3] On June 24, 2013, the Supreme Court ruled 5-4 in favor of Mutual Pharmaceuticals, throwing out the earlier $21 million jury verdict.[4]

Cite to:

Bartlett v. Mut. Pharm. Co., Inc., 678 F.3d 30, 34 (1st Cir. 2012).

References

  1. ↑ Scheper MA, Nikitakis NG, Chaisuparat R, Montaner S, Sauk JJ (March 2007). "Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma". Neoplasia 9 (3): 192–9. doi:10.1593/neo.06781. PMC 1838577. PMID 17401459.
  2. ↑ Shiff SJ, Qiao L, Tsai LL, Rigas B (July 1995). "Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells". J. Clin. Invest. 96 (1): 491–503. doi:10.1172/JCI118060. PMC 185223. PMID 7615821.
  3. ↑ Thomas, Katie. "Justices to Take Up Case on Generic Drug Markers' Liability". New York Times. Retrieved 4 March 2013.
  4. ↑ Kendall, Brent. "Supreme Court Again Limits Product-Liability Suits on Generic Drugs". Wall Street Journal. Retrieved 24 June 2013.

External links