Department of Nephrology, Charité Universitätsmedizin Berlin, Humboldt University, Charité Campus Mitte, Berlin, Germany.
Clin Pharmacokinet. 2012 Oct 1;51(10):661-9. doi: 10.1007/s40262-012-0003-z.
Aliskiren represents a novel class of orally active renin inhibitors. This study analyses the pharmacokinetics, tolerability and safety of single-dose aliskiren inpatients with end-stage renal disease (ESRD) undergoing haemodialysis.
Six ESRD patients and six matched healthy volunteers were enrolled in an open-label, parallel-group, single-sequence study. The ESRD patients underwent two treatment periods where 300 mg of aliskiren was administered 48 or 1 h before a standardized haemodialysis session (4 h, 1.4 m(2) high-flux filter, blood flow 300 mL/min, dialysate flow 500 mL/min). Washout was >10 days between both periods. Blood and dialysis samples were taken for up to 96 h postdose to determine aliskiren concentrations.
Compared with the healthy subjects (1681 ± 1034 ng·h/mL), the area under the plasma concentration-time curve (AUC) from time zero to infinity was 61% (haemodialysis at 48 h) and 41% (haemodialysis at 1 h) higher in ESRD patients receiving single-dose aliskiren 300 mg. The maximum (peak) plasma drug concentration (481 ± 497 ng/mL in healthy subjects) was 17% higher (haemodialysis at 48 h) and 16% lower (haemodialysis at 1 h). In both treatment periods, dialysis clearance was below 2% of oral clearance and the mean fraction eliminated from circulation was 10 and 12% in period 1 and 2, respectively. Drug AUCs were similar in ESRD patients receiving aliskiren 1 or 48 h before dialysis. No severe adverse events occurred.
The exposure of aliskiren is moderately higher in ESRD patients. Only a minor portion is removed by a typical haemodialysis session. Aliskiren exposure is not significantly affected by intermittent haemodialysis, suggesting that no dose adjustment is necessary in this population.
阿利吉仑是一种新型的口服肾素抑制剂。本研究分析了终末期肾病（ESRD）患者单次给予阿利吉仑的药代动力学、耐受性和安全性，这些患者正在接受血液透析。
纳入 6 例 ESRD 患者和 6 例匹配的健康志愿者，进行一项开放标签、平行组、单序列研究。ESRD 患者接受了两个治疗期，在 4 小时、1.4 m2高通量滤器、血流 300 mL/min、透析液流量 500 mL/min 的标准化血液透析前 48 小时或 1 小时给予 300 mg 阿利吉仑。两个时期之间的洗脱期>10 天。在给药后长达 96 小时内采集血样和透析液样，以确定阿利吉仑浓度。
与健康受试者（1681±1034 ng·h/mL）相比，接受单次 300 mg 阿利吉仑的 ESRD 患者的血浆浓度-时间曲线下面积（AUC）从零时到无穷大分别增加了 61%（血液透析 48 小时）和 41%（血液透析 1 小时）。健康受试者的最大（峰）血浆药物浓度（481±497 ng/mL）增加了 17%（血液透析 48 小时）和 16%（血液透析 1 小时）。在两个治疗期内，透析清除率均低于口服清除率的 2%，在第 1 期和第 2 期，循环中平均消除分数分别为 10%和 12%。在接受阿利吉仑 1 小时或 48 小时前进行血液透析的 ESRD 患者中，药物 AUC 相似。未发生严重不良事件。
阿利吉仑在 ESRD 患者中的暴露程度中等偏高。单次血液透析仅能去除一小部分药物。间歇性血液透析对阿利吉仑的暴露无显著影响，提示该人群无需调整剂量。
