Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism

Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study to test the effect of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100 (apoB-100) in triglyceride-rich lipoprotein (TRL), intermedi...

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Bibliographic Details
Published in:Journal of lipid research Vol. 48; no. 8; pp. 1746 - 1753
Main Authors: Lamon-Fava, Stefania, Diffenderfer, Margaret R, Barrett, P Hugh R, Buchsbaum, Aaron, Matthan, Nirupa R, Lichtenstein, Alice H, Dolnikowski, Gregory G, Horvath, Katalin, Asztalos, Bela F, Zago, Valeria, Schaefer, Ernst J
Format: Journal Article
Language:English
Published: United States Elsevier 01.08.2007
Subjects:
Anticholesteremic Agents - administration & dosage
Anticholesteremic Agents - pharmacology
Apolipoprotein A-I - blood
Apolipoprotein B-100 - blood
Apolipoprotein B-48 - blood
Atorvastatin
campesterol
Cholesterol - blood
Cholesterol - metabolism
Cholesterol, LDL - blood
Cholesterol, LDL - metabolism
Cross-Over Studies
Dose-Response Relationship, Drug
Female
Heptanoic Acids - administration & dosage
Heptanoic Acids - pharmacology
Humans
Kinetics
lathosterol
Male
Middle Aged
Pyrroles - administration & dosage
Pyrroles - pharmacology
Time Factors
Triglycerides - blood
Triglycerides - metabolism
ISSN:0022-2275
Online Access:Get full text
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Summary:Nine hypercholesterolemic and hypertriglyceridemic subjects were enrolled in a randomized, placebo-controlled, double-blind, crossover study to test the effect of atorvastatin 20 mg/day and 80 mg/day on the kinetics of apolipoprotein B-100 (apoB-100) in triglyceride-rich lipoprotein (TRL), intermediate density lipoprotein (IDL), and LDL, of apoB-48 in TRL, and of apoA-I in HDL. Compared with placebo, atorvastatin 20 mg/day was associated with significant reductions in TRL, IDL, and LDL apoB-100 pool size as a result of significant increases in fractional catabolic rate (FCR) without changes in production rate (PR). Compared with the 20 mg/day dose, atorvastatin 80 mg/day caused a further significant reduction in the LDL apoB-100 pool size as a result of a further increase in FCR. ApoB-48 pool size was reduced significantly by both atorvastatin doses, and this reduction was associated with nonsignificant increases in FCR. The lathosterol-campesterol ratio was decreased by atorvastatin treatment, and changes in this ratio were inversely correlated with changes in TRL apoB-100 and apoB-48 PR. No significant effect on apoA-I kinetics was observed at either dose of atorvastatin. Our data indicate that atorvastatin reduces apoB-100- and apoB-48-containing lipoproteins by increasing their catabolism and has a dose-dependent effect on LDL apoB-100 kinetics. Atorvastatin-mediated changes in cholesterol homeostasis may contribute to apoB PR regulation.
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ISSN:0022-2275
DOI:10.1194/jlr.M700067-JLR200