Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
J Clin Pharmacol. 2010 Dec;50(12):1358-66. doi: 10.1177/0091270009359525. Epub 2010 Feb 11.
Gender and body weight influence the pharmacokinetics and pharmacodynamics of many drugs. This pooled analysis of 17 clinical studies evaluated the effect of gender, body mass index (BMI), body weight, and lean body weight (LBW) on the pharmacokinetics of the direct renin inhibitor aliskiren in healthy volunteers (n = 392). A separate pooled analysis of 5 clinical studies in patients with hypertension (n = 2327) assessed the influence of gender and BMI on the effects of aliskiren on plasma renin activity and blood pressure. Area under the aliskiren plasma concentration-time curve (AUC(τ)) was 22% lower and the peak aliskiren plasma concentration (C(max)) was 24% lower in men than women (P < .05). BMI was not significantly correlated with AUC(τ) (r = 0.005; P = .917); AUC(τ) was negatively correlated with body weight (r = -0.235; P < .0001) and LBW (r = -0.295; P < .0001). Results were similar for C(max). Adjusting individual aliskiren AUC(τ) and C(max) values for overall mean body weight or LBW abolished gender differences. Based on r(2) values, LBW variation accounted for 8.9% of aliskiren AUC(τ) variation. In patients with hypertension, gender and BMI did not significantly influence the effects of aliskiren on plasma renin activity or blood pressure. It was concluded that lower systemic exposure to aliskiren in men versus women relates to differences in body weight; neither gender nor body weight has clinically relevant effects on the pharmacokinetics or pharmacodynamics of aliskiren.
性别和体重会影响许多药物的药代动力学和药效学。这项纳入 17 项临床研究的汇总分析评估了性别、体重指数（BMI）、体重和去脂体重（LBW）对健康志愿者中直接肾素抑制剂阿利克仑药代动力学的影响（n=392）。另外一项纳入 5 项高血压患者临床研究的汇总分析评估了性别和 BMI 对阿利克仑对血浆肾素活性和血压影响的影响（n=2327）。男性的阿利克仑血浆浓度-时间曲线下面积（AUC（τ））比女性低 22%，峰阿利克仑血浆浓度（C（max））比女性低 24%（P<0.05）。BMI 与 AUC（τ）无显著相关性（r=0.005；P=0.917）；AUC（τ）与体重（r=-0.235；P<0.0001）和 LBW（r=-0.295；P<0.0001）呈负相关。C（max）的结果相似。校正个体阿利克仑 AUC（τ）和 C（max）值的总体均值体重或 LBW 后，性别差异消失。根据 r（2）值，LBW 变异解释了阿利克仑 AUC（τ）变异的 8.9%。在高血压患者中，性别和 BMI 对阿利克仑对血浆肾素活性或血压的影响无显著影响。结论是，男性与女性相比，阿利克仑的系统暴露量较低与体重差异有关；性别和体重对阿利克仑的药代动力学或药效学均无临床相关影响。
