THE EFFECT OF ORLISTAT ON THE PHARMACOKINETICS OF PHENYTOIN IN HEALTHY-VOLUNTEERS

To assess the effect of an orlistat-induced reduction in dietary fat a bsorption on the pharmacokinetics of phenytoin, a third-parry blind, p lacebo-controlled, randomized, two-way crossover study was performed i n 12 healthy volunteers. Each participant received single 300-mg oral doses of phenytoin administered on the fourth day of treatment with 12 0 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 per iod. Serial blood samples were collected before and up to 96 hours aft er each dose of phenytoin to determine serum concentrations of phenyto in. The 90% confidence intervals (CI) for the ratio of geometric least -squares means for maximum concentration (C-max) and area under the co ncentration-time curve (AUC) and for the difference of arithmetic leas t-squares means for time of maximum concentration (t(max)) and elimina tion 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 1 20 mg three times daily did not significantly alter the pharmacokineti cs of a single 300-mg oral dose of phenytoin in healthy volunteers.