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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1101.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effect of Ezetimibe on the In Vivo Kinetics of ApoB-48 and ApoB-100 in Men With Primary Hypercholesterolemia

André J. Tremblay; Benoît Lamarche; Jeffrey S. Cohn; Jean-Charles Hogue; Patrick Couture

From the Lipid Research Center (A.J.T., B.L., J.-C.H., P.C.), CHUL Research Center, Québec, Canada; the Institute on Nutraceuticals and Functional Foods (B.L.), Laval University, Québec City, Canada; and the Heart Research Institute (J.S.C.), Camperdown, Sydney, NSW Australia.

Correspondence to Patrick Couture, MD, FRCP(C), PhD, Lipid Research Center, CHUL Research Center, 2705 Laurier Boulevard, S-102, Québec, Qc, Canada, G1V 4G2. E-mail patrick.couture{at}crchul.ulaval.ca

Objective— To examine the impact of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on the in vivo kinetics of apolipoproteins (apo) B-48 and B-100 in humans.

Methods and Results— Kinetics of triglyceride-rich lipoprotein (TRL) apoB-48 and very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) apoB-100 labeled with a stable isotope were assessed at baseline and at the end of 8 weeks of treatment with 10 mg/d of ezetimibe in 8 men with moderate primary hypercholesterolemia. Data were fit to a multicompartmental model using SAAMII to calculate fractional catabolic rate (FCR) and production rate (PR). Ezetimibe significantly decreased total and LDL cholesterol concentrations by –14.5% and –22.0% (P=0.004), respectively, with no significant change in plasma triglyceride and high-density lipoprotein (HDL) cholesterol levels. Ezetimibe had no significant effect on TRL apoB-48 kinetics and pool size (PS). However, VLDL and IDL apoB-100 FCRs were significantly increased (+31.2%, P=0.02 and +20.8%, P=0.04, respectively) with a concomitant elevation of VLDL apoB-100 PR (+20.9%, P=0.04). Furthermore, LDL apoB-100 PS was significantly reduced by –23.2% (P=0.004), caused by a significant increase in FCR of this lipoprotein fraction (+24.0%, P=0.04).

Conclusions— These results indicate that reduction of plasma LDL cholesterol concentration after treatment with ezetimibe is associated with an increase in FCR of apoB-100–containing lipoproteins.

Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, has been shown to decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. To determine mechanism, apolipoprotein B kinetic studies were conducted in 8 hypercholesterolemic men. Reduction of LDL-C concentrations after treatment with ezetimibe was mainly associated with an increase in fractional catabolic rate of apoB-100–containing lipoproteins

Key Words: apolipoprotein B-48 • apolipoprotein B-100 • cholesterol absorption • ezetimibe • gas chromatography/mass spectrometry • intestine • kinetic

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