Apejuwe

LCZ696 (Sacubitril/Valsartan), ti o ni Valsartan (ARB) ati Sacubitril (AHU377) ni 1: 1 molar ratio, jẹ ẹya akọkọ-ni-kilasi, ẹnu bioavailable, ati meji-angiotensin receptor-neprilysin (ARN) inhibitor fun haipatensonu. ati ikuna ọkan [1][2][3]. LCZ696 ṣe atunṣe cardiomyopathy dayabetik nipasẹ didi iredodo, aapọn oxidative ati apoptosis.

abẹlẹ

LCZ696 jẹ akọkọ ni kilasi ARNi (inhibitor neprilysin receptor angiotensin) ti o ni awọn ẹya anionic ti AR valsartan ati prodrug neprilysin inhibitor AHU377 (1: 1 ratio) fun ikuna ọkan ati haipatensonu.

Awọn olugba angiotensin jẹ awọn olugba G-protein-papọ. Wọn ṣe agbedemeji eto inu ọkan ati ẹjẹ ati awọn ipa miiran ti angiotensin II eyiti o jẹ peptide bioactive ti eto renin-angiotensin. Neprilysin jẹ endopeptidase didoju ti o dinku awọn peptides vasoactive endogenous gẹgẹbi awọn peptides natriuretic. Idinamọ ti neprilysin ṣe alekun ifọkansi peptides natriuretic ti o ṣe alabapin si ọkan, iṣọn-ẹjẹ ati aabo kidirin. [1]

Ninu awọn eku Sprague-Dawley, iṣakoso ẹnu ti LCZ696 yori si iwọn-igbẹkẹle iwọn lilo ni ajẹsara ti peptide natriuretic ti atrial ti o waye lati idinamọ neprilysin. Ninu awọn eku transgenic ilọpo meji haipatensonu, LCZ696 fa iwọn-igbẹkẹle ati idinku idaduro ni titẹ iṣọn-alọ ọkan. Awọn olukopa ti o ni ilera, aileto kan, afọju-meji, iwadii iṣakoso ibibo jẹrisi pe LCZ696 pese idinamọ neprilysin nigbakanna ati idena olugba AT1. LCZ696 jẹ ailewu ati faramọ daradara ninu eniyan. [2] [3]

Awọn itọkasi:
McMurray JJ, Packer M, Desai AS et al. Idilọwọ Angiotensin-neprilysin dipo enalapril ni ikuna ọkan. N Engl J Med. 2014 Oṣu Kẹsan 11; 371 (11): 993-1004.
Gu J, Noe A, Chandra P, Al-Fayoumi S et al. Pharmacokinetics ati pharmacodynamics ti LCZ696, aramada meji-angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol. 2010 Kẹrin; 50 (4): 401-14.
Langenickel TH, Dole WP. Angiotensin receptor-neprilysin inhibition with LCZ696: ọna aramada fun itọju ikuna ọkan, Drug Discov Today: Ther Strategies (2014) .

Ibi ipamọ

Ilana kemikali