| Item |
Information |
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Drug Groups
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approved |
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Description
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Sulindac is a nonsteroidal anti-inflammatory agent (NSAIA) of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIAs, it may be used in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in vivo to an active sulfide compound by liver enzymes. The sulfide metabolite then undergoes enterohepatic circulation; it 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 NSAIA's except for drugs of the cyclooxygenase-2 (COX-2) inhibitor class. The exact mechanism of its NSAIA properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis. |
| Indication |
For acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis. |
| Pharmacology |
Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities. |
| Toxicity |
Acute oral toxicity (LD50) in rats is 264 mg/kg. Cases of overdose have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdose: stupor, coma, diminished urine output and hypotension. |
| Affected Organisms |
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Humans and other mammals |
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| Biotransformation |
Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur. |
| Absorption |
Approximately 90% absorbed in humans following oral administration. |
| Half Life |
The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours. |
| Protein Binding |
At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin. |
| Elimination |
Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway. |
| Clearance |
* Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)] |
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