title: Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia.
abstract: Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion of a stable isotope in the fed state. The coadministration of simvastatin and ezetimibe significantly reduced plasma concentrations of cholesterol (-43.0%), LDL-C (-53.6%), and triglycerides (-44.0%). Triglyceride-rich lipoproteins (TRL) apoB-48 pool size (PS) was significantly decreased (-48.9%) following combination therapy mainly through a significant reduction in TRL apoB-48 production rate (PR) (-38.0%). The fractional catabolic rate (FCR) of VLDL and LDL apoB-100 were significantly increased with all treatment modalities compared with placebo, leading to a significant reduction in the PS of these fractions. We also observed a positive correlation between changes in TRL apoB-48 PS and changes in TRL apoB-48 PR (r = 0.85; P < 0.0001) with combination therapy. Our results indicate that treatment with simvastatin plus ezetimibe is effective in reducing plasma TRL apoB-48 levels and that this effect is most likely mediated by a reduction in the intestinal secretion of TRL apoB-48. Our study also indicated that the reduction in LDL-C concentration following combination therapy is mainly driven by an increase in FCR of apoB-100 containing lipoproteins.
authors.affiliation: Lipid Research Center, CHUL Research Center, Québec City, Québec, Canada.
authors.forename: André J
authors.initials: AJ
authors.lastname: Tremblay
authors.forename: Benoît
authors.initials: B
authors.lastname: Lamarche
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Hogue
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
mesh_terms: D000328:Adult; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000378:metabolism*; D001384:Azetidines / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D010919:Placebos / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001384:Azetidines; D008078:Cholesterol, LDL; D008074:Lipoproteins; D010919:Placebos; D014280:Triglycerides; D019821:Simvastatin; D000069438:Ezetimibe