Influence of orlistat on the regulation of gallbladder contraction in man: a randomized double-blind placebo-controlled crossover study.

Details

Serval ID
serval:BIB_5265
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Influence of orlistat on the regulation of gallbladder contraction in man: a randomized double-blind placebo-controlled crossover study.
Journal
Digestive Diseases and Sciences
Author(s)
Froehlich F., Hartmann D., Guezelhan C., Gonvers J.J., Jansen J.B., Fried M.
ISSN
0163-2116 (Print)
ISSN-L
0163-2116
Publication state
Published
Issued date
1996
Peer-reviewed
Oui
Volume
41
Number
12
Pages
2404-2408
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Orlistat (tetrahydrolipstatin) is a potent inhibitor of gastric and pancreatic lipase activity causing a diminution of free fatty acids in the intestinal lumen. The release of cholecystokinin (CCK) critically depends on the presence of free fatty acids in the small intestine. Postprandial CCK release and gallbladder contraction might be decreased by orlistat, potentially resulting in an increased risk of gallstone formation. In this double-blind, placebo-controlled, six-way crossover study, six healthy volunteers ingested in a randomized order three isocaloric test meals (250 ml) of identical osmolality with either orlistat (200 mg) or placebo: (a) a pure-fat meal (25 g triglycerides), (b) a mixed meal containing fat (8 g; 29% of caloric content), protein (10 g; 17%), and dextrose (32 g; 54%), and (c) a fat-free meal containing albumin (25 g; 46%) and dextrose (32 g; 54%). Gallbladder volumes were determined by ultrasonography, and plasma CCK, pancreatic polypeptide and gastrin levels by RIA. Gall-bladder contraction (AUC, % x 90 min; difference of means +/- 95% CI) in subjects receiving orlistat or placebo did not significantly differ after intake of the pure-fat meal (443+/-1174), the mixed meal (313+/-1170), or the fat-free-meal (-760+/-1180). The release of CCK (AUC; pM x 90 min; difference of means +/- 95% CI) was not different between orlistat and placebo after ingestion of the pure-fat meal (-18+/-64), the mixed meal (-45+/-62), and the fat-free meal (27+/-63). Likewise, the release of pancreatic polypeptide and gastrin was similar after intake of the meals with either orlistat or placebo. A single dose of orlistat did not reduce gallbladder motility after ingestion of meals with differing fat contents. The safety of long-term treatment with orlistat with respect to gallstone formation remains to be determined.
Keywords
Adult, Area Under Curve, Cholecystokinin/blood, Cross-Over Studies, Dietary Fats/administration & dosage, Double-Blind Method, Fasting/physiology, Female, Gallbladder Emptying/drug effects, Gastrins/blood, Humans, Lactones/blood, Lactones/pharmacology, Lipase/antagonists & inhibitors, Male, Pancreatic Polypeptide/blood, Reference Values
Pubmed
Web of science
Create date
19/11/2007 12:41
Last modification date
20/08/2019 14:07
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