The effect of pravastatin in relation to low density lipoprotein receptor activity

Current Medical Research and Opinion
H HayashiS Miyazaki

Abstract

Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, suppresses new synthesis of cholesterol via HMG-CoA in hepatocytes. As a result, low density lipoprotein (LDL) receptor activity in the liver is enhanced, which leads to lowering of plasma cholesterol. Inhibitors are shown to be effective in heterozygous familial hypercholesterolaemia (FH). Although FH heterozygotes are defined genetically as possessing half the normal LDL receptor activity, some heterogeneity of LDL receptor activity is observed in these patients. To see whether the effect of an inhibitor is related to LDL receptor activity in each patient, pravastatin was administered to 7 FH heterozygotes for 3 months at a daily dose of 10 mg; their mean LDL receptor activities measured before the therapy were 45.0 +/- 9.9% of the normal control. After medication, mean serum total cholesterol decreased from 349.0 to 279.7 mg/dl (p less than 0.05), and LDL-cholesterol decreased from 272.6 to 207.7 mg/dl (p less than 0.05). A significant correlation between the initial LDL receptor activity and the effect of pravastatin was not proved. However, the pre-treatment level of LDL-cholesterol was positively correlated (r = 0.795) with the absolut...Continue Reading

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