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Effect of ezetimibe on the in vivo kinetics of apoB-48 and apoB-100 in men with primary hypercholesterolemia.

Tremblay, André J; Lamarche, Benoît; Cohn, Jeffrey S; Hogue, Jean-Charles; Couture, Patrick.
Arterioscler Thromb Vasc Biol; 26(5): 1101-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16528005


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.


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).


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.
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