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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mechanisms of action in the liver of crilvastatin, a new hydroxymethylglutaryl-coenzyme A reductase inhibitor.

Crilvastatin is a drug from the pyrrolidone family that had been shown to induce non-competitive inhibition of rat hydroxymethylglutaryl-coenzyme A reductase activity in vitro. The aim of this study was to evaluate the activity of crilvastatin on the hepatic metabolism of cholesterol in rats. Crilvastatin increased low density lipoprotein (LDL)-cholesterol uptake by the liver more than high density lipoprotein (HDL) uptake, thus increasing by up 30% the clearance of excess plasma cholesterol. In normolipidemic rats, crilvastatin significantly enhanced acyl coenzyme A:cholesterol acyl transferase and cholesterol 7 alpha-hydroxylase activity. In rats with a previous high cholesterolemia, crilvastatin also enhanced cholesterol 7 alpha-hydroxylase activity and did not increase liver acyl coenzyme A:cholesterol acyl transferase activity. These findings suggest that a drug such as crilvastatin could have a hypocholesterolemic effect by a mechanism other than the sole inhibition of cholesterol synthesis, possibly by stimulating cholesterol and bile salt secretion via the biliary tract in previously hypercholesterolemic rats.[1]


  1. Mechanisms of action in the liver of crilvastatin, a new hydroxymethylglutaryl-coenzyme A reductase inhibitor. Clerc, T., Jomier, M., Chautan, M., Portugal, H., Senft, M., Pauli, A.M., Laruelle, C., Morel, O., Lafont, H., Chanussot, F. Eur. J. Pharmacol. (1993) [Pubmed]
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