Hippokratia 1998, 2(4):165-173
D. Panidis, A. Kourtis
Gastric and pancreatic lipases are enzymes that play a pivotal role in the digestion of dietary fat. Orlistat, a semi-synthetic 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 tract. Orlistat acts by binding covaientiy to the serin 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 monoacyl glycerides and free fatty acids. This effect can be measured using 24h fecal fat excretion as a representative pharmacodynamic parameter, orlistat taken with an appropriate diet promotes clinically significant weight loss and reduces weight gain in obese patients over a 2-year period. The use of orlistat beyond two years needs careful monitoring with respect to efficacy and adverse events.