Influence of Gemfibrozil and Clofibrate on Metabolism of Cholesterol and Plasma Triglycerides in Man

Mechanisms for the hypolipidemic action of gemfibrozil were examined in seven patients with hypertriglyceridemia. In addition, seven hyperlipidemic patients were studied with and without clofibrate treatment to compare the mechanisms by which these two drugs lower plasma triglyceride levels. All patients were studied on a metabolic ward. The first month was a control period, followed by one month of either gemfibrozil or clofibrate therapy. During treatment with gemfibrozil, plasma total triglyceride levels decreased by an average of 51%, and triglyceride levels in very low-density lipoproteins (VLDLs) fell by 57%. Transport rates of VLDL triglyceride were determined by multicompartmental analysis following injection of tritiated glycerol as a precursor. Gemfibrozil decreased transport (production) of VLDL triglyceride by an average of 28% and increased the fractional catabolic rate (FCR) of VLDL triglyceride by 92%. Clofibrate reduced plasma total triglyceride values on an average of 32% and VLDL triglyceride values by 38%. In contrast to gemfibrozil, clofibrate did not change transport rates of VLDL triglyceride but increased the fractional catabolic rate of VLDL triglyceride by 35%. Gemfibrozil thus decreased production of VLDL triglyceride and enhanced its clearance, while clofibrate only increased clearance of VLDL triglyceride. On the average, plasma cholesterol levels did not fall during gemfibrozil treatment, but levels of cholesterol in high-density lipoproteins and in low-density lipoproteins increased by 31% and 11%, respectively. The drug produced a 30% increase in fecal excretion of neutral steroids and a 37% decrease in fecal excretion of bile acids. Outputs of total neutral steroids and net cholesterol balance thus remained unchanged.