Influence of simvastatin on apoB-100 secretion in non-obese subjects with mild hypercholesterolemia.
Statins decrease apoB-100-containing lipoproteins by increasing their fractional catabolic rates through LDL receptor-mediated uptake. Their influence on hepatic secretion of these lipoproteins is controversial. The objective of the study was to examine the influence of simvastatin on the secretion of apoB-100-containing lipoproteins in fasting non-obese subjects. Turnover of apoB-100-containing lipoproteins was investigated using stable isotope-labeled tracers. Multicompartmental modeling was used to derive kinetic parameters. Eight male subjects (BMI 25 +/- 3 kg/m(2)) with mild hypercholesterolemia (LDL cholesterol 135 +/- 30 mg/dL) and normal triglycerides (111 +/- 44 mg/dL) were examined under no treatment (A), under chronic treatment with simvastatin 40 mg/day (B) and after an acute-on-chronic dosage of 80 mg simvastatin under chronic simvastatin treatment (C). Lipoprotein concentrations changed as expected under 40 mg/day simvastatin. Fractional catabolic rates increased in IDL and LDL but not in VLDL fractions versus control [VLDL +35% in B (n.s.) and +21% in C (n.s.); IDL +169% in B (P = 0.08) and +187% in C (P = 0.032); LDL +87% in B (P = 0.025) and +133% in C (P = 0.025)]. Chronic (B) and acute-on-chronic simvastatin treatment (C) did not affect lipoprotein production rates [VLDL -8 and -13%, IDL +47 and +38%, and LDL +19 and +30% in B and C, respectively (all comparisons n.s.)]. The data indicate that simvastatin does not influence the secretion of apoB-100-containing lipoproteins in non-obese subjects with near-normal LDL cholesterol concentrations.
Berthold
Heiner K
HK
Department of Clinical Pharmacology, University of Bonn, Bonn, Germany. heiner.berthold@charite.de
Mertens
Jessica
J
Birnbaum
Julia
J
Brämswig
Susanne
S
Sudhop
Thomas
T
Barrett
P Hugh R
PH
von Bergmann
Klaus
K
Gouni-Berthold
Ioanna
I
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D018592:Cross-Over Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D008078:Cholesterol, LDL; D019821:Simvastatin
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