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.
Melia
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Hoffmann-La Roche, Inc., Nutley, New Jersey 07110-1199, USA.
Mulligan
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TE
Zhi
J
J
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*
D000927:Anticonvulsants; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D007783:Lactones; D010672:Phenytoin; D000077403:Orlistat