Mutual Suppression of the Uricosuric Effects of Sulfinpyrazone and Salicylate: a Study in Interactions between Drugs.

A striking example of antagonistic drug effects (2) is afforded by the observation that in man salicylate, itself uricosuric in high dose, inhibits the pronounced uricosuria produced by probenecid (3, 4), sulfinpyrazone1 (5-9), and zoxazolamine (9-11). This suppressive action of salicylate has been assumed to be due to its successful competition with these drugs, and with uric acid, for renal tubular transport; one aspect of this competition is expressed as inhibition of tubular secretion of uric acid by small (and large) doses of salicylate, which partially counterbalances the inhibition of tubular reabsorption of uric acid produced by uricosuric agents (12). The present study provides experimental support for the operation of these mechanisms, but indicates that the interactions at least of salicylate and sulfinpyrazone are even more complex, involving competition also for binding sites on transporting plasma proteins, and possibly elsewhere. The consequences of the interplay of competition at these various sites are described in man, and also in the dog, in which mutual suppression of the uricosuric effects of sulfinpyrazone and salicylate, so apparent in man, could not be demonstrated.