title: Rosuvastatin Enhances the Catabolism of LDL apoB-100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner.
abstract: Dose-associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B-100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA-I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB-100 production rate (PR), as well as increase apoB-100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB-100 in TRL and LDL and apoA-I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography-mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54% (both P < 0.0001), triacylglycerol by 14% (ns) and 35% (P < 0.01), apoB by 30 and 36% (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA-I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB-100 FCR by 36 and 46% (both ns) and LDL apoB-100 by 63 and 102% (both P < 0.05), respectively. HDL apoA-I PR increased with low dose rosuvastatin (12%, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB-100 PR or HDL apoA-I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB-100, with no significant effects on apoB-100 production or HDL apoA-I kinetics.
authors: Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
authors: Ngoc-Anh
authors: NA
authors: Le
authors: Margaret R
authors: MR
authors: Diffenderfer
authors: Nuntakorn
authors: N
authors: Thongtang
authors: Esther M M
authors: EM
authors: Ooi
authors: P Hugh R
authors: PH
authors: Barrett
authors: Katalin V
authors: KV
authors: Horvath
authors: Gregory G
authors: GG
authors: Dolnikowski
authors: Bela F
authors: BF
authors: Asztalos
authors: Ernst J
authors: EJ
authors: Schaefer
authors: W Virgil
authors: WV
authors: Brown
mesh_terms: D053299:Apolipoprotein B-100 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage* / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D014280:Triglycerides; C032607:low density lipoprotein triglyceride; D000068718:Rosuvastatin Calcium