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

• Published in: European journal of clinical pharmacology 1998-11, Vol.54 (9-10), p.773-777
• Main Authors: MELIA, A. T, ZHI, J, ZELASKO, R, HARTMANN, D, GÜZELHAN, C, GUERCIOLINI, R, ODINK, J
• Format: Article
• Language: English
• Subjects: Adult; Area Under Curve; Biological and medical sciences; Central Nervous System Depressants - pharmacokinetics; Central Nervous System Depressants - pharmacology; Diet; Dietary Fats - metabolism; Digestive system; Double-Blind Method; Drug Interactions; Drug therapy; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - pharmacology; Ethanol; Ethanol - pharmacokinetics; Ethanol - pharmacology; Feces - chemistry; Half-Life; Humans; Hypolipidemic Agents - pharmacokinetics; Hypolipidemic Agents - pharmacology; Intestinal Absorption - drug effects; Lactones - pharmacokinetics; Lactones - pharmacology; Lipase - antagonists & inhibitors; Male; Medical sciences; Orlistat; Pharmacology. Drug treatments
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s002280050550

The primary objective was to investigate the possible interference of ethanol on the orlistat effect on inhibition of dietary fat absorption and the possible interference of orlistat on the pharmacokinetics of ethanol. Secondary objectives were to assess the tolerability during concomitant dosing of orlistat and ethanol and to determine the ethanol effect on plasma levels of orlistat. 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 run-in period to accustom subjects to a standardized diet of 2500 kcal/day (30% fat) and to establish baseline fecal fat excretion was followed by a 6-day treatment period. Subjects were randomly assigned to one of three treatment groups (A = orlistat 120 mg t.i.d. and ethanol placebo, B = orlistat 120 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 determination of ethanol serum concentrations at specified times over 5 h after each dose of ethanol on days -1 and 6, and for determination of orlistat plasma concentrations on days 1, 3, 5, and 6. Feces were collected quantitatively on days -5 through 8 for analysis of fecal fat. The means of baseline-corrected fecal fat excretion values were comparable: 23.7 g for group A (orlistat) and 22.7 g for group B (orlistat and ethanol). No significant difference was found regarding ethanol pharmacokinetic parameters between treatments with orlistat and placebo. No apparent differences existed between the number of plasma samples with measurable orlistat concentrations in groups A and B. Concomitant ingestion of social amounts of ethanol did not alter the inhibitory effect of orlistat on dietary fat absorption during short-term treatment (6 days) with orlistat. Short-term treatment with orlistat had no significant influence on ethanol pharmacokinetics.