EFFECT ON DIETARY-FAT ABSORPTION OF ORLISTAT, ADMINISTERED AT DIFFERENT TIMES RELATIVE TO MEAL INTAKE

Orlistat (O) is a potent and selective inhibitor of gastrointestinal l ipases. The effect on dietary fat absorption following dosing of O at different times relative to meals was investigated in a placebo (P) co ntrolled study in 24 hospitalized healthy males. After a 5-day run-in, to accustom the subjects to a diet of 2400 kcal and 77 g fat per day and to establish baseline faecal fat excretion, subjects received, in four parallel groups of 6, over 8 days three times daily doses of 80 m g O, P, P (group A) or P, 80 mg O, P (group B) or P, P, 80 mg O (group C) or P, P, P (group D) at mid-meal, 1 h and 2 h after mid-meal respe ctively. Faeces were collected to measure total fat excretion. The mea n (s.d.) of faecal fat in percent of dietary fat. after deduction of p re-treatment faecal fat, was 32.8 (8.1), 34.0 (8.8), 26.9 (4.0) and -1 .4 (1.7) in groups A, B, C and D respectively. It was concluded that, within the time period investigated, the pharmacological effect of O i s not critically dependent on the time of dosing relative to meals.