The pravastatin-induced decrease of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis in humans

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have b een reported to suppress biliary cholesterol secretion and saturation. It r emains unproven whether this is mediated by inhibition of cholesterol synth esis. Therefore, the effect of a long-term administration of pravastatin on cholesterogenesis and on biliary lipid secretion was investigated in seven healthy volunteers. Placebo or 40 mg of pravastatin were taken daily at be dtime for 5 weeks using a double-blind crossover design. During the last we ek, 12 hours after the last drug intake 0.04 mmol [1-C-13]acetate/kg.h and 0.5 g polyethylene glycol 4,000/h were infused intraduodenally for 15 hours . Plasma and duodenal bile samples were collected hourly. Thereafter, the d ecay of [C-13]labeled plasma cholesterol was measured during the following 3 days. The fractional and absolute syntheses of plasma and biliary cholest erol were determined by gas chromatography mass spectrometry using mass iso topomer distribution analysis. At the end of the pravastatin period plasma total and low-density lipoprotein (LDL) cholesterol had decreased by 20% an d 24%, respectively. Similarly, pravastatin suppressed biliary secretion ra tes of cholesterol, total bile acids and phospholipids (P <.05) by 46%, 36% , and 51%. As a consequence, cholesterol saturation index remained unchange d. However, fractional syntheses of cholesterol were comparable (P >.05) on placebo compared with pravastatin with 3.1% versus 4.0% in plasma and 4.3% versus 5.2% in bile after 15 hours, respectively. The mean absolute synthe sis rates amounted to 0.3 mg/kg/h on placebo versus 0.4 on pravastatin (P > .05), In conclusion, the pravastatin-induced reduction of biliary cholester ol secretion is not directly related to an inhibition of cholesterol synthe sis.