Peking Union Medical College Hospital, Beijing, China.
Clin Drug Investig. 2010;30(4):221-8. doi: 10.2165/11533050-000000000-00000.
Aliskiren is the first oral direct renin inhibitor to be approved for the treatment of hypertension. The pharmacokinetic and pharmacodynamic profile of aliskiren has been extensively characterized in Caucasian individuals; however, drug disposition, treatment response and tolerability can vary among ethnic groups, and these variations are difficult to predict.
To evaluate the single- and multiple-dose pharmacokinetics of aliskiren in healthy Chinese subjects.
This was a randomized, single-blind, parallel-group, placebo-controlled study. On day -1, subjects were randomized to one of four cohorts (aliskiren 75, 150, 300 or 600 mg). On day 1, eight individuals in each cohort received a single dose of active treatment and two received placebo. Subjects randomized to aliskiren 300 mg received additional once-daily doses on days 5-11 to establish steady-state pharmacokinetics. Subjects receiving aliskiren 75, 150 or 600 mg (cohorts 1, 2 and 4) completed the study at the end of the 96-hour pharmacokinetic assessment period. Subjects receiving aliskiren 300 mg (cohort 3) had additional pharmacokinetic assessments on days 5-15. The study was carried out at the Peking Union Medical College Hospital, Beijing, China, and included 40 healthy Chinese subjects. The main outcome measures were the pharmacokinetic parameters for aliskiren, including area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) and maximum plasma concentration (C(max)).
Aliskiren AUC(infinity) and C(max) increased greater than proportionally across the 8-fold dose range (75-600 mg; mean AUC(infinity) 291-4726 ng x h/mL, mean C(max) 62-699 ng/mL), but a dose-proportional 2-fold increase was observed within the clinically approved dose range (150-300 mg; mean AUC(infinity) 876-1507 ng x h/mL, mean C(max) 137-271 ng/mL).
At steady state, the mean AUC during the dosage interval (AUC(tau)) for aliskiren 300 mg (1532 +/- 592 ng x h/mL) was similar to the AUC(infinity) observed following a single dose. Aliskiren exhibits similar single-dose and steady-state pharmacokinetics in Chinese subjects compared with those observed in Caucasian individuals in previous studies.
阿利吉仑是首个被批准用于治疗高血压的口服直接肾素抑制剂。阿利吉仑的药代动力学和药效学特征已在白种人群中得到广泛描述；然而，药物处置、治疗反应和耐受性在不同种族之间可能存在差异，这些差异难以预测。
评估阿利吉仑在健康中国受试者中的单剂量和多剂量药代动力学。
这是一项随机、单盲、平行组、安慰剂对照研究。于-1 天，受试者被随机分配至四个队列之一（阿利吉仑 75、150、300 或 600mg）。于 1 天，每个队列中的 8 名受试者接受单次剂量的活性治疗，2 名受试者接受安慰剂。接受阿利吉仑 300mg 的受试者在第 5-11 天接受额外的每日一次剂量以建立稳态药代动力学。接受阿利吉仑 75、150 或 600mg（队列 1、2 和 4）的受试者在 96 小时药代动力学评估期结束时完成研究。接受阿利吉仑 300mg（队列 3）的受试者在第 5-15 天进行额外的药代动力学评估。该研究在中国北京的北京协和医学院医院进行，共纳入 40 名健康中国受试者。主要观察指标为阿利吉仑的药代动力学参数，包括从零时到无穷大的血浆浓度-时间曲线下面积（AUC(无穷大)）和最大血浆浓度（C(max)）。
阿利吉仑 AUC(无穷大)和 C(max)在 8 倍剂量范围内呈大于比例增加（75-600mg；平均 AUC(无穷大)291-4726ng·h/mL，平均 C(max)62-699ng/mL），但在临床批准剂量范围内观察到 2 倍剂量比例增加（150-300mg；平均 AUC(无穷大)876-1507ng·h/mL，平均 C(max)137-271ng/mL）。
在稳态下，阿利吉仑 300mg 的剂量间隔期间的平均 AUC（AUC(tau)）（1532±592ng·h/mL）与单次剂量后观察到的 AUC(无穷大)相似。与之前在白种人群中观察到的情况相比，阿利吉仑在中国受试者中的单剂量和稳态药代动力学相似。
