Effect of lifibrol on the metabolism of low density lipoproteins and cholesterol

Gloria L Vega, K. Von Bergmann, Scott M Grundy, Sarah D Blumenschein, N. B. Carter, P. Laeis, B. Lindenthal, J. Von Bergmann, A. Simatupang, D. Lutjohann, Beverley A Huet

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Lifibrol is a powerful cholesterol-lowering drug of unknown mechanism of action. This investigation was carried out to determine whether the major action of lifibrol is to enhance clearance of low density lipoproteins (LDL) through the LDL-receptor pathway, and if so, whether the drug exerts its action by altering the excretion of bile acids (acidic steroids), the absorption of cholesterol, or the synthesis of cholesterol. In a first study, in two patients with complete absence of LDL receptors, lifibrol therapy had essentially no effect on plasma LDL concentrations; in two others who had a marked reduction in LDL-receptor activity, response to the drug was attenuated. These findings suggest that lifibrol requires an intact LDL- receptor pathway to exert its action. In a second study, in patients with primary moderate hypercholesterolemia, isotope kinetic studies showed that lifibrol enhanced the fractional catabolic rate of LDL-apolipoprotein B (apo B), but had no effect on transport rates of LDL; these observations likewise support the probability that lifibrol acts mainly to increase the activity of the LDL-receptor pathway. However, in a third study in hypercholesterolemic patients, lifibrol therapy failed to increase acidic steroid excretion, inhibit cholesterol absorption, or reduce net cholesterol balance. Furthermore, lifibrol treatment did not significantly reduce urinary excretion of mevalonic acid. In contrast, in a parallel study, simvastatin therapy, which is known to inhibit cholesterol synthesis; gave the expected decrease in net cholesterol balance and reduction in urinary excretion of mevalonic acid. Thus, lifibrol, like statins, appears to increase the activity of LDL receptors; but in contrast to findings with statins, it was not possible to detect a significant decreased synthesis of cholesterol, either from balance studies or from urinary excretion of mevalonic acid. This finding raises the possibility that lifibrol activates the LDL-receptor pathway through a different mechanisms which remains to be determined.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of Internal Medicine
Volume246
Issue number1
DOIs
Publication statusPublished - 1999

    Fingerprint

Keywords

  • Apolipoprotein metabolism
  • Hypercholesterolemia
  • Lifibrol

ASJC Scopus subject areas

  • Internal Medicine

Cite this