INFLUENCE OF DIETARY-COMPOSITION ON THE INHIBITION OF FAT-ABSORPTION BY ORLISTAT

Orlistat, a potent and selective inhibitor of gastrointestinal lipases , is designed for the treatment of obesity. The effect of orlistat on dietary fat absorption, when it was administered with diets differing in fibre content (high and low) and accessibility of fat (intra- and e xtracellular fat), was investigated in 32 hospitalized healthy males, according to an open, two-factorial study design. The subjects were ra ndomly allocated to one of four parallel groups of equal size: A = int racellular fat, high fibre (28 g/day); B extracellular fat, high fibre ; C = extracellular fat, low fibre (9 g/day); or D = intracellular fat , low fibre. After a 5-day run-in period to accustom the volunteers to the standardized diet (2500 kcal and 84 g fat per day) and to establi sh baseline faecal fat parameters, they received 80 mg orlistat, three times daily mid-way through each meal for 8 days. Faeces were collect ed to measure total fat and fi ee fatty acid excretions. The mean base line-corrected excretion (% of dietary fat) in groups A, B, C and D), respectively, was 37.0, 30.4, 30.3 and 34.5 for total fat, and 6.5, 4. 3, 2.6 and 3.9 for free fatty acids. The 95% confidence intervals for the difference between the means for high fibre and low fibre groups a nd for intracellular fat and extracellular fat groups, respectively, w ere 1.4 +/- 4.9 and 5.5 +/- 4.9 for total fat, and 2.2 +/- 3.1 and 1.9 +/- 3.1 for free fatty acids. The statistically significant differenc e (P < 0.05) in total faecal fat between intracellular fat and extrace llular fat groups, in absolute terms < 5 g fat/day, was not regarded a s clinically relevant. Under the conditions of this study, dietary fib re content and accessibility of fat had no relevant effect on the inhi bition of fat absorption by orlistat.