Pharmacokinetic aspects of the interaction of sulfonamides with ibuprofen or mepirizole in dogs.

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Abstract
Interactions between 2 sulfonamides and ibuprofen or mepirizole were investigated in dogs by pharmacokinetic analysis. When sulfamethizole was coadministered with an acidic nonsteroidal antiinflammatory agent, ibuprofen, the .beta.-elimination half-life (t1/2 (.beta.)) for sulfamethizole was increased .apprx. 10 times compared to the control; the coadministration of sulfamethizole with a basic agent, mepirizole, resulted in slightly prolonged or unchanged t1/2 (.beta.) compared to the control. In the case of sulfanilamide, the time course of plasma level was not altered by coadministration of either antiinflammatory agent. An attempt was made to elucidate the mechanism by which ibuprofen alters the pharmacokinetics of sulfamethizole. In renal clearance experiments, the clearance ratio of sulfamethizole was markedly decreased after ibuprofen infusion. No significant alteration of protein binding of sulfamethizole was found when ibuprofen was added to dog plasma. The increased terminal t1/2 of sulfamethizole caused by ibuprofen may be mainly a result of competitive interactions between them at the renal secretory level.