|
Xenical: Pharmacokinetics
Absorption
In normal weight and obese volunteers, the systemic exposure to Xenical (Orlistat) was minimal. Plasma concentrations of intact Orlistat were nearly non-measurable (< 5 ng/ml) following a single oral administration of 360 mg orlistat.
In general, after long-term treatment at therapeutic doses, detection of intact Orlistat in plasma was sporadic and concentrations were extremely low (<10 ng/ml or 0.02 microM), without evidence of accumulation showing consistency with negligible absorption.
Distribution
The volume of distribution cannot be determined because Xenical (Orlistat) is minimally absorbed. In vitro Orlistat is > 99% bound to plasma proteins (lipoproteins and albumin were the major binding proteins). Orlistat minimally partitions into erythrocytes.
Metabolism
Based on animal data, it is likely that the metabolism of Orlistat occurs mainly presystemically. Two major metabolites accounted for approximately 42% of the total radioactivity in plasma resulting from the minute fraction of the dose that was absorbed systemically in obese patients.
These two major metabolites have very weak lipase inhibitory activity (1000- and 2500-fold less than Orlistat respectively). In view of this low inhibitory activity and the low plasma levels at therapeutic doses (average of 26 ng/ml and 108 ng/ml respectively), these metabolites are pharmacologically inconsequential. >>>
Xenical: Pharmacokinetics - more info
|
