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Journal of Lipid Research, Vol. 50, 2117-2123, October 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men

Thomas Sudhop^1,*, Michael Reber^1,*, Diane Tribble, Aditi Sapre, William Taggart, Patrice Gibbons, Thomas Musliner, Klaus von Bergmann^* and Dieter Lütjohann^2,*

^* Institute of Clinical Chemistry and Pharmacology, University of Bonn, Bonn, Germany
Institute of Clinical Chemistry and Pharmacology, Merck Research Laboratories, Rahway, NJ

² To whom correspondence should be addressed. e-mail: dieter.luetjohann{at}ukb.uni-bonn.de

This study evaluates changes in cholesterol balance in hypercholesterolemic subjects following treatment with an inhibitor of cholesterol absorption or cholesterol synthesis or coadministration of both agents. This was a randomized, double blind, placebo-controlled, four-period crossover study to evaluate the effects of coadministering 10 mg ezetimibe with 20 mg simvastatin (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to either drug alone or placebo in 41 subjects. Each treatment period lasted 7 weeks. Ezetimibe and ezetimibe/simvastatin decreased fractional cholesterol absorption by 65% and 59%, respectively (P < 0.001 for both relative to placebo). Simvastatin did not significantly affect cholesterol absorption. Ezetimibe and ezetimibe/simvastatin increased fecal sterol excretion (corrected for dietary cholesterol), which also represents net steady state cholesterol synthesis, by 109% and 79%, respectively (P < 0.001). Ezetimibe, simvastatin, and ezetimibe/simvastatin decreased plasma LDL-cholesterol by 20, 38, and 55%, respectively. The coadministered therapy was well tolerated. The decreases in net cholesterol synthesis and increased fecal sterol excretion yielded nearly additive reductions in LDL-cholesterol for the coadministration of ezetimibe and simvastatin.

Supplementary key words cholesterol balance • cholesterol absorption and synthesis • ezetimibe simvastatin combination

Abbreviations: CI, confidence interval; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride

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