Orlistat

Orlistat is a drug used for the treatment of obesity. Its main effect is to prevent the absorption of fats from the human diet, which leads to a reduction in calorie intake. It should always be combined with a reduced calorie diet supervised by a physician. Orlistat is indicated in patients with a BMI > 30 and in patients with a BMI > 28 who also have certain weight-related risk factors.

Orlistat is a derivative of lipstatin, a potent natural inhibitor of human pancreatic lipases. The substance is semisynthetically produced from lipstatin isolated from the bacterium Streptomyces toxytricini. It was first approved by the U.S. Food and Drug Administration in 1999.

Pharmacodynamics

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.

Pharmacokinetics

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.

Drug Interactions

• 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.

Side effects

The primary side effects of the drug are limited to the gastrointestinal tract and include steatorrhea (oily, loose stools), fecal incontinence, and frequent or urgent bowel movements. Absorption of fat-soluble vitamins and other fat-soluble nutrients is inhibited by taking orlistat.

Contraindications

Orlistat is contraindicated in:

• Malabsorption
• hypersensitivity to orlistat
• impaired gallbladder function (e.g., after cholecystectomy)
• Pregnancy and lactation
• Anorexia and bulimia

Caution is advised especially in cases of obstructed bile ducts, impaired liver function and pancreatic diseases. Here, use is recommended only after detailed consideration of the cost-benefit risk.