1.
Is age an important factor for vascular response to statin therapy? A serial optical coherence tomography and intravascular ultrasound study.
Dai, J, Hou, J, Xing, L, Jia, H, Hu, S, Soeda, T, Minami, Y, Ong, D, Vergallo, R, Zhang, S, et al
Coronary artery disease. 2017;(3):209-217
Abstract
OBJECTIVE Age-related structural and functional changes in vessel wall may affect the time course of vascular response to statin therapy. In this study, we sought to compare the response of lipid-rich plaque to statin therapy in elderly versus younger patients using optical coherence tomography and intravascular ultrasound. PATIENTS AND METHODS Sixty-nine patients who underwent serial optical coherence tomography and intravascular ultrasound at the time point of baseline, 6, and 12 months were divided into two groups according to median age: group A (age<57 years, n=35) and group B (age≥57 years, n=34). Patients were treated with intensive (atorvastatin 60 mg/day) or moderate (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) statin therapy. RESULTS A continuous increase in fibrous-cap thickness (FCT) from baseline to 12 months was observed in both groups (P<0.001, <0.001, respectively). Intensive statin induced greater percent change in FCT at 12 months than moderate statin in group B (P=0.020), but not in group A (P=0.251). Mean lipid arc decreased significantly at 12 months in two groups (P<0.001, <0.001, respectively), and this response was delayed for 6 months (P=0.403) and began to decrease during the second 6 months (P<0.001) in group B. Normalized total atheroma volume decreased significantly in group A (P<0.001), but not in group B (P=0.349). CONCLUSION Statin therapy could stabilize lipid-rich plaque irrespective of age, and intensive statin therapy was more effective than a moderate dose of statin in increasing FCT, particularly in older patients. A delayed response of lipid content and unfavorable change in normalized total atheroma volume to statin were observed in elderly patients.
2.
Pharmacokinetics of simvastatin lactone and its active metabolite simvastatin hydroxy acid in healthy Chinese male and female volunteers.
Yang, W, Xu, H, Song, Y, Wang, X, Ren, X, Zhao, D, Cai, Y, Zhang, S, Huang, J, Zhang, LR, et al
International journal of clinical pharmacology and therapeutics. 2014;(2):151-8
Abstract
BACKGROUND Gender differences in pharmacokinetics have been reported to have important clinical consequences; however, no information about differences in the pharmacokinetics of the cholesterol-lowering drug simvastatin lactone and its metabolite, simvastatin hydroxy acid, in males and females is available. OBJECTIVE The aim of this study was to investigate the effect of gender on the pharmacokinetics of simvastatin lactone and simvastatin hydroxy acid in healthy Han Chinese volunteers. METHODS 16 healthy volunteers (8 males and 8 females) were orally administered a single dose of 40 mg simvastatin lactone after an overnight fast. Plasma was then collected 24 hours after simvastatin lactone administration. Concentrations of simvastatin lactone and simvastatin hydroxy acid were measured by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). RESULTS There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender. For simvastatin hydroxy acid, peak plasma concentrations (Cmax) and dose-normalized by the subject weight Cmax (NCmax) were higher in females than in males. Furthermore, NCmax and dose-normalized by the subject weight AUC (NAUC0-24h, NAUC0-∞) ratios of simvastatin hydroxy acid to simvastatin lactone in females were higher than in males. CONCLUSION This study indicates that gender affects the plasma concentrations of active simvastatin hydroxy acid, but has no significant effect on parent simvastatin lactone. Raised plasma concentrations of simvastatin hydroxy acid in females may enhance the risk of systemic adverse effects during simvastatin lactone treatment.