Orlistat fails to alter postprandial plasma lipid excursions or plasma lipases in normal-weight male volunteers

OBJECTIVES: After 10 d of orlistat administration (120 mg three times/day), the primary objective was to determine the drug's effect on postprandial plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities on day 10 after an oral fat-load. The secondary objectives were to determine the effects of orlistat on 12 h postprandial measures of: (1) preheparin HTGL and LPL; and (2) serum triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and free fatty acids. METHODS: Twenty-four normal-weight, healthy male volunteers were randomized to either 120 mg orlistat (n = 12) or placebo (n = 12) three times a day with meals for 10 d. Preheparin LPL and HTGL activities and LPL specific activity were measured in the fasted state on days 1, 5, and 10. On days 5 and 10 the study medication (orlistat or placebo) was taken at the beginning of a fat-rich breakfast and serum lipid and lipoprotein levels monitored for 12 h postprandially. On day 10, 15 min postheparin HTGL activity was measured 8 h after the fat-rich breakfast. RESULTS: No differences were found between groups in fasting levels of preheparin LPL or HTGL activity or in LPL-specific activity on days 1, 5 and 10. No difference was found between the two treatment groups in postheparin HTGL activity 8 h after the fat-rich breakfast. Also, no differences were found between the two groups in plasma triglycerides or lipoproteins. CONCLUSION: The results indicate that the oral administration of orlistat (120 mg t.i.d.) does not significantly alter plasma triglycerides or lipoproteins, and that the inhibitory effect of orlistat on lipases is limited to the gastrointestinal tract and is not manifested systemically.