腦啡肽酶屬于一種中性肽鏈內切酶, 其受到抑制可以提高利鈉肽、緩激肽和P物質的生物活性, 引起利尿、血管舒張和抗細胞增殖, 進而產(chǎn)生明顯的減輕心臟負荷和降低血壓作用。LCZ696是諾華公司開發(fā)的第一個血管緊張素Ⅱ受體-腦啡肽酶雙重抑制劑, 由纈沙坦和sacubitril按物質的量1:1共結晶組成, 美國FDA于2014年7月已接受了它作為治療射血分數(shù)降低心力衰竭(HFrEF)的新藥申請。主要對LCZ696的基礎藥學、作用機制、藥理作用以及臨床治療心力衰竭的有效性、安全性和耐受性等做一簡述。

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.

天津市應用基礎與前沿技術研究計劃重點項目(14JCZDJC33500)