The interaction of the lipase inhibitor orlistat with ethanol in healthy volunteers

Objectives: The primary objective was to investigate the possible interfere nce of ethanol on the orlistat effect on inhibition of dietary fat absorpti on and the possible interference of orlistat on the pharmacokinetics of eth anol. Secondary objectives were to assess the tolerability during concomita nt dosing of orlistat and ethanol and to determine the ethanol effect on pl asma levels of orlistat. Methods: This was a double-blind, placebo-controlled, parallel, randomized study performed in 30 (three parallel groups of ten subjects each) healthy normal weight male subjects between the ages of 20 and 30 years. A 5-day ru n-in period to accustom subjects to a standardized diet of 2500 kcal/day (3 0% fat) and to establish baseline fecal fat excretion was followed by a 6-d ay treatment period. Subjects were randomly assigned to one of three treatm ent groups (A = orlistat 120 mg t.i.d. and ethanol placebo, B = orlistat 12 0 mg t.i.d. and 40 g ethanol qd on days -1 and 6, and 40 g bid on days 1-5, and C = orlistat placebo tid and 40 g ethanol qd on days -1 and 6, and 40 g b.i.d. on days 1-5). Serial blood samples were collected for determinatio n of ethanol serum concentrations at specified times over 5 h after each do se of ethanol on days -1 and 6, and for determination of orlistat plasma co ncentrations on days 1, 3, 5, and 6. Feces were collected quantitatively on days -5 through 8 for analysis of fecal fat. Results: The means of baseline-corrected fecal fat excretion Values were co mparable: 23.7 g for group A (orlistat) and 22.7 g for group B (orlistat an d ethanol). No significant difference was found regarding ethanol pharmacok inetic parameters between treatments with orlistat and placebo. No apparent differences existed between the number of plasma samples with measurable o rlistat concentrations in groups A and B. Conclusion: Concomitant ingestion of social amounts of ethanol did not alte r the inhibitory effect of orlistat on dietary fat absorption during short- term treatment (6 days) with orlistat. Short-term treatment with orlistat h ad no significant influence on ethanol pharmacokinetics.