The effect of different sulfonamides on phenytoin metabolism in man

Acta Med Scand Suppl. 1979;624:106-10. doi: 10.1111/j.0954-6820.1979.tb00729.x.


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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Female
  • Half-Life
  • Humans
  • Liver / metabolism
  • Male
  • Middle Aged
  • Phenytoin / blood
  • Phenytoin / metabolism*
  • Sulfonamides / pharmacology*


  • Sulfonamides
  • Phenytoin