Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia

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Abstract

Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was used for treatment of 12 patients with moderate hypercholesterolemia, but not classical familial hypercholesterolemia. For most patients, measurements of turnover of low density lipoprotein-apolipoprotein B (LDL-apoB) were made on placebo and during treatment with two doses of mevinolin. LDL turnover was determined after injection of autologous 125I-labeled radioiodinated LDL. Compared to placebo, a low dose of mevinolin (10 mg, twice daily (BID)) caused reductions of plasma total cholesterol and LDL-cholesterol averaging 15% and 20%, respectively; corresponding reductions on high doses of mevinolin (20 mg BID) were 22% and 31%, respectively. Triglyceride levels were unchanged by the drug. High density lipoprotein cholesterol levels rose significantly on the high dose, but not on the low dose. Neither dose produced a statistically significant change in fractional catabolic rate (FCR) for LDL-apoB for the whole group, although several patients had increases in FCR on both doses. In contrast, both doses of mevinolin caused decreases in production rates of LDL-apoB. Thus the fall in LDL levels in patients with moderate hypercholesterolemia can be explained more by a reduction in the input rate of LDL-apoB than by enhanced fractional removal of LDL from the circulation.

Original languageEnglish (US)
Pages (from-to)1464-1475
Number of pages12
JournalJournal of lipid research
Volume26
Issue number12
StatePublished - Dec 1 1985

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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