Hitoshi Sekikawa

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

Interactions between two sulfonamides and ibuprofen or mepirizole were investigated in dogs by pharmacokinetic analysis. When sulfamethizole was coadministered with an acidic non-steroidal anti-inflammatory agent, ibuprofen, the β-elimination half-life (t1/2 (β)) for sulfamethizole was increased approximately 10 times compared to the control, whereas the coadministration of sulfamethizole with a basic agent, mepirizole, resulted in slightly prolonged or unchanged t1/2 (β) 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. These results suggest that the increased terminal half-life of sulfamethizole caused by ibuprofen is mainly a result of competitive interactions between them at the renal secretory level.