Comparative study of interactions between 4-biphenylacetic acid and sulfamethizole, and between fenbufen and sulfamethizole in rats.

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Abstract
The effects of fenbufen and 4-biphenylacetic acid (a pharmacologically active metabolite of fenbufen) on the plasma level of sulfamethizole were investigated in rats. The persistence of sulfamethizole in plasma was remarkably prolonged by coadministration of fenbufen and moderately prolonged by coadministration of 4-biphenylacetic acid.In the renal clearance experiments, the clearance ratio of sulfamethizole was greatly decreased after 4-biphenylacetic acid infusion, in accordance with the result for fenbufen reported previously. It is speculated that prolongation of the persistence of sulfamethizole in plasma by fenbufen or 4-biphenylacetic acid is mainly caused by competitive interactions between sulfamethizole and fenbufen or 4-biphenylacetic acid at the renal secretory level. The lesser effect of 4-biphenylacetic acid in prolonging the plasma level of sulfamethizole as compared with that of fembufen might be attributed to rapid biotransformation of 4-biphenylacetic acid. In a protein binding experiment, fenbufen and 4-biphenylacetic acid were found to displace sulfamethizole bound to rat plasma protein, but the displacing activities were quite weak as compared with those of ibuprofen and bucolome.
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