Abstract
Clofibrate has gained widespread attention as an effective agent for type IIb, III and IV hyperlipoproteinemias. In the patients with familial hypercholesterolemia, conventional agents such as clofibrate have been known to be less effective in reducing serum cholesterol level, but probucol is more effective. We studied the effects of clofibrate and probucol on serum lipoprotein levels in man and the reducing mechanism of LDL and HDL in cholesterol-fed rabbits.
Clofibrate caused a significant reduction in the levels of VLDL-cholesterol, VLDL-triglyceride and IDL-cholesterol, and an increase of HDL-cholesterol in primary hypercholesterolemic patients. Probucol reduced the levels of LDL and HDL-cholesterol in familial hypercholesterolemic patients, and reductions of tuberous xanthomas and xanthelasmas were noted. These results indicate that probucol is an effective agent for the treatment of patients with familial hypercholesterolemia.
To study the reducing mechanisms of LDL and HDL, probucol was administered to cholesterolfed rabbits and radioisotope-labelled LDL or HDL was injected intravenously. Probucol did not cause a change in the fractional catabolic rate of apoLDL, apoHDL and esterified cholesterol of HDL. These results indicate that the inhibition in the synthesis of LDL and HDL may contribute to the reduction of serum LDL and HDL.
