Inkcazo

I-LCZ696 (i-Sacubitril / i-Valsartan), iqulethwe i-Valsartan (i-ARB) kunye ne-Sacubitril (i-AHU377) kwi-1: i-molar ratio ye-1, i-first-in-class, i-bioavailable yomlomo, kunye ne-angiotensin receptor-neprilysin (ARN) inhibitor ye-hypertension. kunye nokusilela kwentliziyo [1][2][3]. I-LCZ696 iphucula i-cardiomyopathy yesifo seswekile ngokuthintela ukuvuvukala, uxinzelelo lwe-oxidative kunye ne-apoptosis.

Imvelaphi

I-LCZ696 ngowokuqala kwiklasi ye-ARNi (i-angiotensin receptor neprilysin inhibitor) equka i-anionic moieties ye-AR valsartan kunye ne-neprilysin inhibitor prodrug AHU377 (1: 1 ratio) ngenxa yokungaphumeleli kwentliziyo kunye noxinzelelo lwegazi.

I-angiotensin receptors zi-G-protein-coupled receptors. Balamla kwi-cardiovascular kunye nezinye iziphumo ze-angiotensin II eyi-bioactive peptide yenkqubo ye-renin-angiotensin. I-Neprilysin yi-endopeptidase engathathi hlangothi ethoba i-endogenous vasoactive peptides efana ne-natriuretic peptides. Ukuvinjelwa kwe-neprilysin kwandisa i-peptides ye-natriuretic yoxinaniso olufake isandla kwintliziyo, i-vascular and renal protection. [1]

Kwiigundane ze-Sprague-Dawley, ulawulo lomlomo lwe-LCZ696 lukhokelela ekunyukeni kokuxhomekeka kwedosi kwi-immunoreactivity ye-atrial natriuretic peptide ebangelwa yi-neprilysin inhibition. Kwiigundane ze-hypertensive eziphindwe kabini ze-transgenic, i-LCZ696 ibangele ukuxhomekeka kwe-dose kunye nokunciphisa okuqhubekayo kwi-arterial pressure. Abathathi-nxaxheba abanempilo, i-randomized, i-double-blind-blind, i-placebo-controlled controlled study iqinisekisile ukuba i-LCZ696 ibonelele nge-inhibition ye-neprilysin efanayo kunye ne-AT1 receptor blockade. I-LCZ696 yayikhuselekile kwaye inyamezeleke kakuhle ebantwini. [2] [3]

IiReferensi:
McMurray JJ, Packer M, Desai AS et al. I-Angiotensin-neprilysin inhibition ngokuchasene ne-enalapril kwi-heart failure. N Ngesi J Med. 2014 Sep 11; 371 (11): 993-1004.
UGu J, uNoe A, uChandra P, uAl-Fayoumi S et al. I-Pharmacokinetics kunye ne-pharmacodynamics ye-LCZ696, inoveli ye-angiotensin receptor-neprilysin inhibitor (ARNi) inoveli. J Clin Pharmacol. 2010 Epreli;50(4):401-14.
Langenickel TH, Dole WP. I-Angiotensin receptor-neprilysin inhibition kunye ne-LCZ696: indlela entsha yonyango lokungaphumeleli kwentliziyo, iDrug Discov Today: Ther Strategies (2014),

Ugcino

Ubume beMichiza