Effect of Ezetimibe on the in vivo kinetics of ApoB-48 and ApoB-100 in men with primary hypercholesterolemia

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.