Pharmacokinetics And Metabolism

About 90% of the drug is absorbed after oral administration (Table 26-1). Peak concentrations of sulindac in plasma are attained within 1-2 hours, while those of the sulfide metabolite occur ~8 hours after the oral administration of sulindac.

Sulindac is oxidized to the sulfone and then reversibly reduced to the active sulfide by the action of bowel microflora on sulindac excreted in the bile.

The t122 of sulindac is ~7 hours, but the active sulfide has a t122 as long as 18 hours. Sulindac and its metabolites undergo extensive enterohepatic circulation, and all are bound extensively to plasma protein.

Little of the sulfide (or of its conjugates) is found in urine. The principal components excreted in the urine are the sulfone and its conjugates, which account for nearly 30% of an administered dose; sulindac and its conjugates account for ~20%. Up to 25% of an oral dose may appear as metabolites in the feces.

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