Pharmacological Properties
Orlistat is a reversible inhibitor of gastric and pancreatic lipases; its mechanism of action results in an inhibition of dietary fat absorption of 30% at the approved dosage. It is generally associated with a loss of fat mass in obese adults and adolescents, as well as decreases in levels of the regulatory hormone leptin as patients lose bodyweight. Vitamin levels are not consistently affected with orlistat use, with only β-carotene and vitamin D and E levels shown to be significantly decreased by orlistat administration in at least one study. Mineral levels are also not affected in obese adolescent patients. Orlistat is effective in improving factors involved or implicated in the pathogenesis of cardiovascular disease.
The absorption of orlistat is minimal in both healthy adult volunteers and adult obese patients. Orlistat is not extensively metabolised, with 83% of excreted orlistat found to be intact drug. Accumulation of orlistat is minimal in both short-and long-term studies. Orlistat is excreted primarily via the faeces.
Because orlistat is minimally absorbed, it has a generally favourable drug-interaction profile. Only the pharmacokinetics of ciclosporin (cyclosporin) and amiodarone have been shown to be affected by coadministration with orlistat. The bioavailability of oral contraceptives in women receiving orlistat who experience severe diarrhoea may be reduced.