脑啡肽酶属于一种中性肽链内切酶, 其受到抑制可以提高利钠肽、缓激肽和P物质的生物活性, 引起利尿、血管舒张和抗细胞增殖, 进而产生明显的减轻心脏负荷和降低血压作用。LCZ696是诺华公司开发的第一个血管紧张素Ⅱ受体-脑啡肽酶双重抑制剂, 由缬沙坦和sacubitril按物质的量1:1共结晶组成, 美国FDA于2014年7月已接受了它作为治疗射血分数降低心力衰竭(HFrEF)的新药申请。主要对LCZ696的基础药学、作用机制、药理作用以及临床治疗心力衰竭的有效性、安全性和耐受性等做一简述。

Neprilysin is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, which can induce natriuretic, vasodilatatory, and anti-proliferative effects. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. LCZ696 (valsartan/sacubitril) is the first angiotensin II receptor-neprilysin inhibitor developed by Novartis. FDA approved a submission for a rolling new drug application and granted fast track designation for LCZ696 in July 2014 for the indication of heart failure and a reduced ejecion fraction (HFrEF). This review discusses the basic pharmacy, mechanism of action, pharmacokinetics properties, pharmacodynamics, clinical efficacy, safety, and tolerability of LCZ696 in treatment of heart failure from the available trials.

天津市应用基础与前沿技术研究计划重点项目(14JCZDJC33500)