The Effect of Orlistat on the Pharmacokinetics of Phenytoin in Healthy Volunteers

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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 (λg) 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.