title: The effect of orlistat on the pharmacokinetics of phenytoin in healthy volunteers.
abstract: 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.
authors.affiliation: Hoffmann-La Roche, Inc., Nutley, New Jersey 07110-1199, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Melia
authors.forename: T E
authors.initials: TE
authors.lastname: Mulligan
authors.forename: J
authors.initials: J
authors.lastname: Zhi
mesh_terms: D000042:Absorption; D000328:Adult; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018565:Food-Drug Interactions; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000077403:Orlistat; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000927:Anticonvulsants; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D007783:Lactones; D010672:Phenytoin; D000077403:Orlistat