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Influence of orlistat on the regulation of gallbladder contraction in man

A randomized double-blind placebo-controlled crossover study

  • Pancreatic And Biliary Disorders
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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. Gallbladder contraction (AUC, % × 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 × 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.

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Authors and Affiliations

  1. From the Gastroenterology Department, University Medical Outpatient Department PMU, Lausanne, Switzerland

    F. Froehlich, D. Hartmann, C. Guezelhan, J. J. Gonvers, J. B. M. J. Jansen & M. Fried

  2. Hoffmann-La Roche Ltd., Basel, Switzerland

    F. Froehlich, D. Hartmann, C. Guezelhan, J. J. Gonvers, J. B. M. J. Jansen & M. Fried

  3. the University of Nijmegen, Nijmegen, The Netherlands

    F. Froehlich, D. Hartmann, C. Guezelhan, J. J. Gonvers, J. B. M. J. Jansen & M. Fried

  4. the Gastroenterology Department, University of Zurich, Zurich, Switzerland

    F. Froehlich, D. Hartmann, C. Guezelhan, J. J. Gonvers, J. B. M. J. Jansen & M. Fried

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  1. F. Froehlich
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  2. D. Hartmann
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  3. C. Guezelhan
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  4. J. J. Gonvers
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  5. J. B. M. J. Jansen
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  6. M. Fried
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Froehlich, F., Hartmann, D., Guezelhan, C. et al. Influence of orlistat on the regulation of gallbladder contraction in man. Digest Dis Sci 41, 2404–2408 (1996). https://doi.org/10.1007/BF02100135

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  • DOI: https://doi.org/10.1007/BF02100135

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