Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in human

William S. Harris, Carlos A. Dujovne, Klaus von Bergmann, James Neal, Jack Akester, Sheryl L. Windsor, Douglas Greene, Zee Look

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

A common pharmacologic approach to lowering elevated serum cholesterol levels has been to interfere with intestinal sterol absorption. Inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) should produce this effect. In this study, we examined the effects of CL 277,082, N-(2,4-difluorophenyl)-N-(4neopentylbenzyl) N-(n-heptyl)urea, an ACAT inhibitor, on cholesterol metabolism in humans. Eight healthy male volunteers were given a placebo for 14 days, followed by 750 mg/day CL 277,082 for 20 days in a single-blind, crossover design. Subjects were studied in a hospital research unit and were fed strictly controlled diets. Cholesterol absorption was measured by the dual isotope method during the final week of both the placebo and the drug phases. Sterol balance was also assessed during these two periods by measuring cholesterol intake, and fecal neutral and acidic sterol excretion rates. Plasma lipids and lipoproteins were measured at the end of each period. The drug was well tolerated and produced no detectable clinical or laboratory side effects. Cholesterol absorption, sterol excretion rates, and plasma lipoprotein levels were all unaffected by treatment. We conclude that CL 277,082 may not interfere with ACAT activity or cholesterol absorption in humans at the doses given under the conditions tested in this study.

Original languageEnglish (US)
Pages (from-to)189-194
Number of pages6
JournalClinical pharmacology and therapeutics
Volume48
Issue number2
DOIs
StatePublished - Aug 1990

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Harris, W. S., Dujovne, C. A., Bergmann, K. V., Neal, J., Akester, J., Windsor, S. L., Greene, D., & Look, Z. (1990). Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in human. Clinical pharmacology and therapeutics, 48(2), 189-194. https://doi.org/10.1038/clpt.1990.134