Orlistat

Orlistat is a lipase inhibitor used as an adjunct to a reduced-calorie diet for the treatment of obesity and overweight in appropriate patients. It promotes weight loss by inhibiting gastric and pancreatic lipases, reducing the absorption of dietary fat from the gastrointestinal tract.

Orlistat is available in both prescription and over-the-counter formulations. When combined with dietary modifications and regular physical activity, it helps achieve and maintain weight loss and may reduce the risk of obesity-related complications.

Orlistat is a reversible inhibitor of gastrointestinal lipases indicated for weight loss and weight maintenance.

Orlistat is indicated for obesity management including weight loss and weight maintenance when used in combination with calorie reduction in overweight and obese adults; this indication applies to both the prescription formulation of 120 mg and the over the counter formulation of 60 mg. Orlistat in the 120 mg prescription formulation is also indicated to reduce the risk for weight regain following weight loss.

• Weight Gain
• Weight Reduction

Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.

Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.

The systemic absorption and exposure of orlistat is low, however, systemic absorption of the drug is not required for orlistat activity. After an oral dose with 360 mg of radiolabeled orlistat, plasma radioactivity achieved a peak at about 8 hours. Plasma concentrations of unchanged parent drug were close to the lower end of detection limits (15

Volume of distribution cannot be obtained because the absorption of orlistat is minimal. Orlistat is minimally distributed to erythrocytes and is primarily bound to proteins.

Orlistat is >99% bound to plasma proteins (mainly lipoproteins and albumin).

After single oral dose of radiolabled orlistat in both normal weight and obese volunteers fecal excretion of the unabsorbed drug was found to be the major route of elimination with 11,20 Fecal elimination of orlistat is estimated between 95-97%. Complete excretion by both routes occurs within in 3 to 5 days.

The half-life of orlistat of the small amount of absorbed orlistat ranges between 1-2 hours.

The oral LD50 of orlistat is >5000 mg/kg in rats. Single orlistat doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been administered to healthy weight and obese subjects without clinically significant adverse findings. In addition, doses of 240 mg three times a day have been given to obese patients for 6 months without a significant adverse effects. Post-marketing reports of overdoses cases indicate no adverse events or adverse events that are similar to those reported with the recommended dose. If a significant overdose with orlistat occurs, the patient should be observed for at least 24 hours. Based on the results of clinical studies, systemic effects caused by orlistat are likely to be rapidly reversible.

• Take with food. Take with meals or up to 1 hour after a meal. Doses may be skipped for missed meals or fat-free meals.