The effect of different sulfonamides on phenytoin metabolism in man

The influence on the metabolism of phenytoin of some sulfonamides given in common clinical doses has been studied. In single dose experiments sulfaphenazole increased phenytoin half-life (T/2) by 237% and decreased phenytoin metabolic clearance rate (MCR) by 67%. Sulfadiazine, sulfamethiazole, sulfamethoxazole + trimethoprim and trimethoprim increased phenytoin T/2 by 80, 66, 39 and 51% respectively, and decreased phenytoin MCR by 45, 36, 27 and 30% respectively. Sulfamethoxazole gave a small but significant increase in phenytoin T/2 but not a corresponding fall in phenytoin MCR. No changes were found in phenytoin T/2 and MCR after treatment with sulfamethoxypyridazine, sulfadimethoxine and sulfamethoxydiazine. Steady state experiments confirmed the findings of the single dose experiments. It is suggested that sulfaphenazole, sulfadiazine, sulfamethizole, sulfamethoxazole + trimethoprim and trimethoprim inhibit hepatic metabolism of phenytoin.