:Sulfaphenazole-induced Elevation of Serum Phenytoin Levels

概要

論文の詳細を見る
Serum phenytoin levels were determined by the GLC technique in 15 epileptic patients, aged 9 to 26 years, taking usual doses of phenytoin for more than 5 years. The levels of this anticonvulsant rose about threefold on 7 to 10 days after adding sulfaphenazo (50 mg/kg daily). In order to investigate the disappearance curve of serum phenytoin, 14C-phenytoin was injected intravenously to rats. From these experiments it was found that the disappearance rate of 14C-phenytoin was markedly prolonged in two rats pretreated with sulfaphenazole (1, 000 mg/kg daily) for 3 days before the experiment, as compared with three control rats. The half-life of 14C-phenytoin was about 90 minutes in control rats while that in sulfaphenazole pretreated rats was more than 240 minutes. When the preparation of rat liver microsomes was used in vitro, parahydroxylation of 14C-phenytoin was inhibited by 44% in the presence of 1 mM sulfaphenazole. These findings suggest that sulfaphenazole inhibits the activity of enzyme hydroxylating phenytoin and may cause the increase of serum phenytoin levels. Consequently sulfaphenazole should be carefully given to epileptic patients taking usual doses of phenytoin.
一般社団法人日本小児神経学会の論文