LCZ696 - CAS 936623-90-4
Catalog number:
Not Intended for Therapeutic Use. For research use only.
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Angiotensin Receptor
LCZ696 is a potent ARNi inhibitor and an investigational drug to treat heart failure. Chemically, LCZ696 is a mixture of valsartan and sacubitril in a 1:1 molar ratio.
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1.Pharmacodynamic and pharmacokinetic profiles of sacubitril/valsartan (LCZ696) in patients with heart failure and reduced ejection fraction.
Kobalava Z1, Kotovskaya Y1, Averkov O1, Pavlikova E1, Moiseev V1, Albrecht D2, Chandra P3, Ayalasomayajula S3, Prescott MF4, Pal P5, Langenickel TH2, Jordaan P2, Rajman I2. Cardiovasc Ther. 2016 Mar 14. doi: 10.1111/1755-5922.12183. [Epub ahead of print]
AIMS: Concomitant renin-angiotensin-aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF.
2.Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects.
Gan L1, Jiang X2, Mendonza A1, Swan T1, Reynolds C2, Nguyen J2, Pal P3, Neelakantham S3, Dahlke M4, Langenickel T4, Rajman I4, Akahori M5, Zhou W2, Rebello S2, Sunkara G2. Clin Pharmacol Drug Dev. 2016 Jan;5(1):27-39. doi: 10.1002/cpdd.181. Epub 2015 Nov 4.
LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%.
3.Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.
Langenickel TH1, Jordaan P2, Petruck J3, Kode K4, Pal P4, Vaidya S5, Chandra P6, Rajman I2. Eur J Clin Pharmacol. 2016 Apr 16. [Epub ahead of print]
PURPOSE: Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization.
4.Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.
Han Y1, Ayalasomayajula S2, Pan W1,3, Yang F1, Yuan Y4, Langenickel T5, Hinder M5, Kalluri S6, Pal P6, Sunkara G7. Eur J Drug Metab Pharmacokinet. 2016 Mar 9. [Epub ahead of print]
BACKGROUND AND OBJECTIVE: Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects.
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CAS 936623-90-4 LCZ696

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