Mode of action of orlistat.

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Guerciolini R

Mode of action of orlistat.

Int J Obes Relat Metab Disord. 1997 Jun;21 Suppl 3:S12-23.

PubMed ID

9225172 [ View in PubMed

]

Abstract

Gastric and pancreatic lipases are enzymes that play a pivotal role in the digestion of dietary fat. Orlistat, a semisynthetic derivative of lipstatin, is a potent and selective inhibitor of these enzymes, with little or no activity against amylase, trypsin, chymotrypsin and phospholipases. It exerts its effect within the gastrointestinal (GI) tract. Orlistat acts by binding covalently to the serine residue of the active site of gastric and pancreatic lipases. When administered with fat-containing foods, orlistat partially inhibits hydrolysis of triglycerides, thus reducing the subsequent absorption of monoaclglycerides and free fatty acids. This effect can be measured using 24h faecal fat excretion as a representative pharmacodynamic parameter. Orlistat's pharmacological activity is dose-dependent and can be described by a simple Emax model which exhibits an initial steep portion of the dose-response curve with a subsequent plateau (approximately 35% inhibition of dietary fat absorption) for doses above 400 mg/d. At therapeutic doses (120 mg tid with main meals) administered in conjunction with a well balanced, mildly hypocaloric diet, the inhibition of fat absorption (approximately 30% of ingested fat) contributes to an additional caloric deficit of approximately 200 calories. Orlistat does not produce significant disturbances to GI physiological processes (gastric emptying and acidity, gallbladder motility, bile composition and lithogenicity) or to the systemic balance of minerals and electrolytes. Similarly, orlistat does not affect the absorption and pharmacokinetics of drugs with a narrow therapeutic index (phenytoin, warfarin, digoxin) or compounds frequently used by obese patients (oral contraceptives, glyburide, pravastatin, slow-release nifedipine).

DrugBank Data that Cites this Article

Drugs

Orlistat

Drug Interactions

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drugs	Interaction
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Alitretinoin Orlistat	Orlistat can cause a decrease in the absorption of Alitretinoin resulting in a reduced serum concentration and potentially a decrease in efficacy.
alpha-Tocopherol acetate Orlistat	Orlistat can cause a decrease in the absorption of alpha-Tocopherol acetate resulting in a reduced serum concentration and potentially a decrease in efficacy.
alpha-Tocopherol succinate Orlistat	Orlistat can cause a decrease in the absorption of alpha-Tocopherol succinate resulting in a reduced serum concentration and potentially a decrease in efficacy.
Beta carotene Orlistat	Orlistat can cause a decrease in the absorption of Beta carotene resulting in a reduced serum concentration and potentially a decrease in efficacy.
D-alpha-Tocopherol acetate Orlistat	Orlistat can cause a decrease in the absorption of D-alpha-Tocopherol acetate resulting in a reduced serum concentration and potentially a decrease in efficacy.