Pharmacokinetics, Safety, and Tolerability of the Oral Renin Inhibitor Aliskiren in Patients With Hepatic Impairment
Pharmacokinetics, Safety, and Tolerability of the Oral Renin Inhibitor Aliskiren in Patients With Hepatic Impairment
复制标题
口服肾素抑制剂阿利吉仑在肝受损患者中的药代动力学、安全性和耐受性
DOI：
10.1177/0091270006294404
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
W. Dole
中科院分区：
文献类型：
--
作者：
S. Vaidyanathan;V. Warren;C. Yeh;M. Bizot;H. Dieterich;W. Dole
Aliskiren是首个用于治疗高血压的口服肾素直接抑制剂。这项开放标签、非随机、单中心、平行组研究比较了轻度、中度或重度肝功能损害患者口服单剂量300mg阿利克仁的药代动力学和安全性。当跨亚组合并时，肝功能损害患者与健康受试者在aliskiren AUC0‐∞（几何平均比，1.12；90%置信区间，0.85,1.48）或Cmax（平均比，1.19；90%置信区间，0.84,1.68）方面无显著差异，肝功能损害严重程度与AUC0‐∞或Cmax均无相关性。Aliskiren在健康受试者和肝功能损害患者中耐受性良好。总之，单剂量给药后，肝损害对阿利克伦的药代动力学没有显著影响，肝病患者不太可能需要调整剂量。
Aliskiren is the first in a new class of orally active, direct renin inhibitors for the treatment of hypertension. This open‐label, nonrandomized, single‐center, parallel‐group study compared the pharmacokinetics and safety of a single 300‐mg oral dose of aliskiren in patients with mild, moderate, or severe hepatic impairment to that in healthy subjects. When pooled across subgroups, there were no significant differences between patients with hepatic impairment and healthy subjects in aliskiren AUC0‐∞ (ratio of geometric means, 1.12; 90% confidence interval, 0.85, 1.48) or Cmax (mean ratio, 1.19; 90% confidence interval, 0.84, 1.68), and there was no correlation between severity of hepatic impairment and either AUC0‐∞ or Cmax. Aliskiren was well tolerated by healthy subjects and patients with hepatic impairment. In conclusion, hepatic impairment has no significant effect on the pharmacokinetics of aliskiren following single‐dose administration, and dosage adjustment is unlikely to be needed in patients with liver disease.