Abstract
The mechanisms for the hypocholesterolemic action of probucol were examined in 17 patients with various levels of plasma cholesterol and triglycerides (TG). All the patients were studied on a metabolic ward. The first period of 6 weeks was for control. Thereafter, probucol was started, and after 2-6 months of drug treatment, the patients were readmitted for another 6-week period for a repeat study. During treatment with probucol, the cholesterol decreased in total plasma by an average of 12%, in low density lipoproteins (LDL) by 11%, and in high density lipoproteins (HDL) by 9%. The TG in total plasma and in very low density lipoproteins (VLDL) remained unchanged during probucol treatment. Turnover of low density lipoprotein apoprotein (apoLDL) was estimated following injection of 125I-labeled apoLDL. Probucol increased the fractional catabolic rate (FCR) for apoLDL by an average of 23%, but did not change apoLDL synthesis. The drug produced no consistent changes in fecal excretion of cholesterol (neutral steroids) and bile acids, in cholesterol absorption, in lipid composition of gallbladder bile, in biliary secretion of cholesterol and bile acids, or in the activities of lipoprotein lipase and hepatic lipase. These data show that probucol lowers LDL by increasing its catabolism. This effect appears to be independent of any changes in metabolism of cholesterol or bile acids.
Highlights
The mechanisms for the hypocholesterolemic action confirmed the lattereffect (17-1 9)
Duringtreatment may be a useful adjunct in treatment of hypercholesterwith probucol, the cholesterol decreased in total plasma by an olemia
Previous reports indicate that patients with types 2a and 2b hyperlipoproteinemia treated with probucol have reductions in plasma cholesterol concentrations ranging from 10 to15%(2- 15)
Summary
The mechanisms for the hypocholesterolemic action confirmed the lattereffect (17-1 9). Other suggested acof probucol were examined in 17 patients with various levels tions are decreased cholesterol absorption and reduced of plasma cholesterol and triglycerides (TG). Duringtreatment may be a useful adjunct in treatment of hypercholesterwith probucol, the cholesterol decreased in total plasma by an olemia. Probucol is easy to take and has few side effects average of 12%,in low density lipoproteins (LDL). Turnover of lowdensity lipoprotein apoprotein (apoLDL) was estimated following inlowering of HDL, probucol-treated subjects have been jection of '451-labeled apoLDL. Probucol increased the fractional reported to have a lower 5-year incidence of sudden death catabolic rate (FCR) for apoLDL by an average of 23%, but and myocardial infarction in a primary prevention did not change apoLDL synthesis.The drugproduced no contrial [25].
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