Effects of clofibrate on cholesterol metabolism.

Abstract

The effects of clofibrate on cholesterol metabolism were studied in one normolipidemic and 5 hyperlipidemic patients by sterol balance methods. In 2 patients, the effects of discontinuation of treatment were also assessed. Clofibrate reduced all classes of plasma lipids. The percentage reduction in triglycerides correlated weil (r = 0.99) with pretreatment levels. On the other hand, percentage reductions in plasma cholesterol, free fatty acids, and phospholipids did not correlate with pretreatment levels but correlated significantly with the fall in plasma triglycerides. In 3 patients, in whom plasma cholesterol was labeled by intravenous infusion of radioactive cholesterol, the specific activity (SA) of plasma cholesterol was determined at frequent intervals. Clofibrate reduced the rate offall ofplasma cholesterol SA while discontinuation of clofibrate increased rate of decline of plasma cholesterol SA. Since clofibrate did not affect the absorption of dietary cholesterol, the changes in plasma cholesterol SA were in all probability related to changes in endogenous synthesis of cholesterol. In addition to the above changes in the specific activity slopes, there were acute increases in plasma cholesterol specific activity which could be explained only by mobilization of tissue cholesterol from the slowly exchangeable pool immediately after the beginning of treatment. The effect of clofibrate on the excretion offecal neutral and acidic steroids was variable and was probably dependent on the balance of its effect on the turnover of plasma lipoproteins on one hand and the mobilization of tissue cholesterol on the other.