Abstract
We have examined the influence of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase on plasma concentrations of lipids and lipoproteins, the rates of cholesterol biosynthesis and degradation of 125I-labelled LDL by freshly isolated mononuclear leucocytes and the 24 h urinary excretion of mevalonic acid in patients with heterozygous familial hypercholesterolaemia. Patients were treated with progressively increasing doses of simvastatin (20, 40, and 80 mg day-1) taken in a twice-daily dosage for a period of 6 weeks on each dose. Plasma concentrations of LDL cholesterol decreased by 36.6%, 45.6% and 47.1% respectively on the three doses. High-affinity degradation of 125I-LDL by freshly isolated mononuclear leucocytes increased significantly on the 20 mg day-1 dosage but no further increase was observed on doses of 40 and 80 mg of simvastatin per day. Rates of 2-14C acetate incorporation into cholesterol by freshly isolated mononuclear leucocytes (obtained 12-15 h after the last dose of simvastatin) increased by 62%, 71% and 29% in cells isolated from patients on 20, 40, and 80 mg day-1 of simvastatin compared with values at baseline. In contrast, the 24 h excretion of mevalonic acid in the ur...Continue Reading
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