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Effect of Xenical (orlistat) 120 mg dose on fat excretion

The relationship between orlistat dose and malabsorption of dietary fat, in subjects consuming a diet containing 20%-30% of calories (50 g-80 g) as fat:

The percentage of ingested fat that is not absorbed, is directly related to drug dose in a curvilinear fashion. At a dose of 360 mg per day (120 mg three times daily with meals), approximately 30% of ingested triglycerides are excreted in stool, which is near the maximum plateau value. Therefore, ingesting more than 120 mg of orlistat with a meal (the prescribed dose) is unlikely to appreciably increase the malabsorption of ingested fat.

It is likely that variability in fat absorption that occurs at any given dose of orlistat is related to how effectively orlistat mixes with the fat content of a meal. Orlistat is more effective in blocking fat absorption from a solid than a liquid meal because preemulsified triglycerides present in a liquid meal are rapidly hydrolyzed by intestinal lipases before significant inhibition by orlistat can occur.
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