Study of interactions between ibuprofen and sulfonamides, and between bucolome and sulfonamides in rats.

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Abstract
In this study, the effects of two non-steroidal anti-inflammatory drugs, ibuprofen and bucolome, on plasma levels of sulfonamides (sulfamethizole and sulfanilamide) were investigated in rats. The persistence of sulfamethizole in plasma was prolonged by coadministration of ibuprofen, while it was hardly affected (though the plasma level was slightly lowered) by coadministration of bucolome. No alteration was observed in the persistence or plasma level of sulfanilamide on coadministration of ibuprofen or bucolome. In experiments to investigate the renal excretion of sulfonamides, the clearance ratio of sulfamethizole was markedly decreased after ibuprofen infusion, while bucolome had little effect. From these results, it is speculated that prolongation of the persistence of sulfamethizole in plasma by ibuprofen is mainly caused by competitive interaction between sulfamethizole and ibuprofen at the renal secretory level. In protein binding experiments, ibuprofen and bucolome were found to displace sulfamethizole bound to rat plasma protein. The displacing activity of bucolome was much stronger than that of ibuprofen. This activity of bucolome may increase the tissue distribution and glomerular filtration of sulfamethizole, and thus influence the plasma level and net renal handling of sulfamethizole.