| 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. |
| Pharmacodynamics |
Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities. |
| Mechanism of action |
Sulindac's exact mechanism of action is unknown. Its
antiinflammatory effects are believed to be due to inhibition of both
COX-1 and COX-2 which leads to the inhibition of prostaglandin
synthesis. Antipyretic effects may be due to action on the hypothalamus,
resulting in an increased peripheral blood flow, vasodilation, and
subsequent heat dissipation. |
| Absorption |
Approximately 90% absorbed in humans following oral administration. |
| Volume of distribution |
Not Available |
| Protein binding |
At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin. |
| Metabolism |
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. |
| Route of 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. |
| 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. |
| Clearance |
- Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]
|
| 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. |
