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- W2410577419 abstract "Probucol is a widely used serum-cholesterol lowering drug. It is proposed that in humans probucol stimulates the plasma clearance of low density lipoproteins (LDL), which accounts for the drug-induced decrease in LDL cholesterol levels. In the liver the enhanced uptake of LDL cholesterol stimulates the conversion of cholesterol into bile acids, which in turn causes an increase in the output of bile acids with the feces. The increased flux through the bile acid biosynthesis pathway tends to deplete the liver pools of cholesterol. This causes stimulation of cholesterol synthesis, which is associated with a higher hepatic efflux of LDL. Thus in humans taking probucol cholesterol turnover is enhanced. In this way a new equilibrium is reached in which LDL production equals LDL catabolism, and in which cholesterol turnover is increased. The probucol-induced reduction in high density lipoprotein (HDL) cholesterol may be caused by inhibition of HDL synthesis. If we assume that the absolute rate of HDL clearance from the plasma is proportional to HDL concentration, then serum HDL will settle at a new, lower level where the clearance rate equals the rate of production. In contrast to humans, probucol may decrease the turnover of cholesterol in rats. The relatively large amounts of probucol generally fed inhibit cholesterol absorption, and this may account for the reduction in serum total cholesterol, which essentially represents HDL cholesterol. The decrease in absorption diminishes intestinal formation of HDL, which in turn leads to a diminished flux of serum cholesterol into the liver, and causes inhibition of bile acid synthesis because substrate availability is depressed. The effect of probucol on cholesterol synthesis is not clear, but the drug must lower the sum of cholesterol absorption and synthesis. In this way, serum cholesterol settles at a new, lower level, where cholesterol input equals its output." @default.
- W2410577419 created "2016-06-24" @default.
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- W2410577419 date "1987-01-01" @default.
- W2410577419 modified "2023-09-23" @default.
- W2410577419 title "Mode of hypocholesterolemic action of probucol in animals and man." @default.
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