Gan, Lu, Langenickel, Thomas Heiko, Petruck, Jesika, Kode, Kiran Kumar, Rajman, Iris, Chandra, Priyamvada, Zhou, Wei, Rebello, Sam and Sunkara, Gangadhar (2016) Effects of age and gender on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor. Journal of Clinical Pharmacology , 56 (1). pp. 78-86. ISSN 00912700

Abstract

LCZ696, a novel angiotensin receptor neprilysin inhibitor, is in development for the treatment of heart failure. Administration of LCZ696 results in systemic exposure to sacubitril (inactive prodrug of LBQ657), LBQ657 (neprilysin inhibitor), and valsartan (angiotensin II receptor blocker). We investigated the potential effect of age and gender on the pharmacokinetics of LCZ696 analytes (LBQ657 and valsartan) in an open-label, single oral dose (400 mg), parallel group study in healthy subjects. Among 36 enrolled subjects, there were 19 male and 17 female subjects; 18 subjects were 18-45 years old (young), and 18 subjects were 65 years of age or older (elderly). Compared to young subjects, the AUCinf and T1/2 for LBQ657 were 42% and 30% greater in elderly subjects, respectively. The Cmax for LBQ657 was similar between age groups. The AUCinf, Cmax, and T1/2 for valsartan were 30%, 24% greater, and 3.35 hours longer in elderly when compared to young subjects, respectively. All pharmacokinetic parameters of LCZ696 analytes (LBQ657 and valsartan) were similar between male and female subjects, indicating no gender effect on the pharmacokinetics of LCZ696 analytes. Considering the magnitude of change and its clinical significance, dose adjustment based on age or gender is not necessary.

Item Type:	Article
Date Deposited:	11 May 2016 23:45
Last Modified:	11 May 2016 23:45
URI:	https://oak.novartis.com/id/eprint/24684