Pharmacokinetic proofs on interaction between zolpidem and phenytoin: A two-treatment, two-period study in healthy male subjects

Abstract

In clinical practice, the simultaneous use of zolpidem and phenytoin cannot always be avoided, although it can be associated with additive depressants effects on the central nervous system. Considering the common metabolic pathways involving CYP3A and CYP2C, a pharmacokinetic interaction between phenytoin and zolpidem is possible, although not previously quantified. The study was designed as a non-randomized, two-period preclinical trial. Twenty male subjects were included in a study consisting of two periods. Between these, subjects were treated for 6 days with a single daily dose of 150 mg phenytoin. For each treatment period, pharmacokinetic parameters of zolpidem were determined. The multiple-dose administration of phenytoin influenced zolpidem’s pharmacokinetics in healthy volunteers, decreasing its exposure through enzymatic induction.