The effect of orlistat on the pharmacokinetics of phenytoin in healthy volunteers.

To assess the effect of an orlistat-induced reduction in dietary fat absorption on the pharmacokinetics of phenytoin, a third-party blind, placebo-controlled, randomized, two-way crossover study was performed in 12 healthy volunteers. Each participant received single 300-mg oral doses of phenytoin administered on the fourth day of treatment with 120 mg orlistat (treatment A) or placebo (treatment B) three times a day for 7 days. The two treatments were separated by a 2-week washout period. Serial blood samples were collected before and up to 96 hours after each dose of phenytoin to determine serum concentrations of phenytoin. The 90% confidence intervals (CI) for the ratio of geometric least-squares means for maximum concentration (Cmax) and area under the concentration-time curve (AUC) and for the difference of arithmetic least-squares means for time of maximum concentration (tmax) and elimination rate constant (lambda z) showed the two treatments of phenytoin to be equal by analysis of variance. An approximately 30% reduction in dietary fat absorption induced by orlistat administered at doses of 120 mg three times daily did not significantly alter the pharmacokinetics of a single 300-mg oral dose of phenytoin in healthy volunteers.