Products By Therapeutical Index
Affecting Nutrition & Metabolism
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Anti-Obesity Agents
OTC Products
Weight Control
Mechanism of Action
Orlislim is a potent, specific, and reversible long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the serine residue of the active site of gastric and pancreatic lipases. The inactivated enzyme is thus unable to hydrolyze dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides. As undigested triglycerides are not absorbed, the resulting caloric deficit has a positive effect on the weight control.
Pharmacokinetics
Based on fecal fat measurements, the effect of Orlistat is seen as soon as 24 to 48 hours after dosing. Upon discontinuation of therapy, fecal fat content usually returns to pre-treatment levels, within 48 to 72 hours.
Absorption
In normal weight and obese volunteers, the systemic exposure to 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 µM), without evidence of accumulation showing consistency with negligible absorption.
Distribution
The volume of distribution cannot be determined because 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 (M1 and M3) 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.
Elimination
Studies in normal weight and obese subjects have shown that fecal excretion of the unabsorbed orlistat was the major route of elimination. Approximately 97% of the administered dose was excreted in faeces and 83% of that as unchanged orlistat.
The cumulative renal excretion of total orlistat-related materials was < 2% of the given dose. The time to reach complete excretion (fecal plus urinary) was 3-5 days. The disposition of orlistat appeared to be similar between normal weight and obese volunteers. Orlistat, M1 and M3 are all subject to biliary excretion.
Pharmacokinetics in special populations
Plasma concentrations of orlistat and its metabolites M1 and M3 were similar in paediatric patients compared to those found in adults at the same dose level. Daily fecal fat excretions were 27% and 7% of dietary intake in orlistat and placebo treatment groups, respectively.
Hepatic and/or renal impairment
Clinical investigations in patients with hepatic and/or renal impairment have not been undertaken.
Each Capsule contains Orlistat 120 mg.
