Vaidyanathan Sujata, Reynolds Christine, Yeh Ching-Ming, Bizot Marie-Noëlle, Dieterich Hans Armin, Howard Dan, Dole William P
Novartis Fharmaceuticals Corporation, East Hanover, New Jersey, USA.
J Clin Pharmacol. 2007 Apr;47(4):453-60. doi: 10.1177/0091270006297921.
This open-label, multicenter study compared the pharmacokinetics and safety of the oral direct renin inhibitor aliskiren in 29 elderly (>or=65 years) and 28 young (18-45 years) healthy subjects. Plasma drug concentrations were determined for up to 168 hours following a single 300-mg oral dose of aliskiren. In elderly compared with young subjects, AUC(0-infinity) was 57% higher (ratio of geometric means 1.57, 90% confidence interval: 1.19, 2.06; P = .008) and C(max) was 28% higher (1.28, 90% confidence interval: 0.91, 1.79; P=.233). Other parameters, including t(max) and Vd/F, were similar between age groups. No differences in aliskiren exposure were observed between subjects ages 65 to 74 years (n=16) and >or=75 years (n=13). Aliskiren was well tolerated by all age groups, including the very elderly. In conclusion, aliskiren exposure is modestly increased in elderly subjects. Based on its wide therapeutic index and shallow dose response for blood pressure lowering, no initial dose adjustment should be needed for elderly patients.
这项开放标签、多中心研究比较了口服直接肾素抑制剂阿利吉仑在29名老年（≥65岁）和28名年轻（18 - 45岁）健康受试者中的药代动力学和安全性。在单次口服300毫克阿利吉仑后，测定长达168小时的血浆药物浓度。与年轻受试者相比，老年受试者的AUC(0 - ∞)高57%（几何均值比为1.57，90%置信区间：1.19, 2.06；P = 0.008），C(max)高28%（1.28，90%置信区间：0.91, 1.79；P = 0.233）。其他参数，包括t(max)和Vd/F，在各年龄组之间相似。在65至74岁（n = 16）和≥75岁（n = 13）的受试者之间未观察到阿利吉仑暴露的差异。所有年龄组，包括高龄老人，对阿利吉仑耐受性良好。总之，老年受试者中阿利吉仑的暴露量适度增加。基于其较宽的治疗指数和对血压降低较浅的剂量反应，老年患者无需进行初始剂量调整。
