Effects of probucol on low density lipoprotein removal and high density lipoprotein synthesis

The possible mechanisms of action of probucol on the metabolism of low density lipoprotein and of high density lipoprotein were studied in 5 hyperlipidaemic subjects. The kinetics of LDL-B protein and of HDL-AI protein were determined by 2-pool analysis of specific radioactivity-time curves after reinjection of 131I-labelled LDL and 125I-labelled HDL at the end of placebo and treatment periods. Probucol increased the fractional removal rate of LDL in 4, an action probably linked to increased bile acid excretion which occurred in all 5 subjects. Nevertheless, the plasma cholesterol concentration fell significantly in only 3. The synthesis of HDL-AI protein fell substantially and was probably responsible for the consistent reduction in plasma apo-AI levels. Thus, probucol appears to enhance LDL-B protein removal and bile acid excretion but inhibits AI protein formation; all these effects may be determined in the small intestine.