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Fibrates and cholelithiasis

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

  • PPAR alpha agonists including clofibrate, bezafibrate or fenofibrate showed an increased risk for cholelithiasis (increase of cholesterol gallstones)
    • however, gemfibrozil appears less lithogenic compared to bezafibrate or clofibrate
  • possible mechanism underlying fibrate-induced lithogenicity could be the increased biliary output of cholesterol and the reduction of bile acid production via the PPAR alpha-mediated down regulation of cholesterol 7alpha-hydroxylase (Cyp7a) and sterol 27-hydroxylase
    • however, based on the relative ability of different PPAR alpha ligands to cause cholelithiasis, other mechanisms contributing to this effect cannot be excluded.

Reference:

  • 1. Rubestrunk A et al. Safety issues and prospects for future generations of PPAR modulators Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2007; 1771 (8): 1065-1081.
  • 2. Mazzella F et al. Effect of gemfibrozil administration on biliary lipid secretion in hyperlipidemic patients. A crossover study with clofibrate, Scand. J. Gastroenterol. 1990;25: 1227-1234.

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