Orlistat acts by inhibiting gastric and pancreatic lipases, enzymes that break down triglycerides in the intestine. When lipase activity is inhibited, dietary triglycerides are no longer broken down into absorbable free fatty acids but are excreted unchanged. This reduces the total amount of fat absorbed by about 30% and promotes weight reduction.
Orlistat has also been found to inhibit the thioesterase domain of fatty acid synthase (FAS), an enzyme involved in the proliferation of certain cancer cells. However, the potential side effects of orlistat, such as inhibition of other cellular off-targets or poor bioavailability, have to date hindered its use as an effective antitumor agent. Orlistat, however, remains a subject of research in this area.
Orlistat is absorbed systemically only in small traces. Because the effect occurs locally in the intestine and absorption is so small, there are no reliable data on pharmacokinetics. The primary route of excretion is via the feces.
- Orlistat may decrease plasma levels of ciclosporin, an immunosuppressant used to prevent transplant rejection. the two drugs should therefore not be administered concomitantly.
- Orlistat may also interfere with the absorption of the antiarrhythmic drug amiodarone.
- It is suspected that orlistat may decrease the absorption of HIV antiretroviral drugs.