title: Effects of age and sex on the pharmacokinetics of LCZ696, an angiotensin receptor neprilysin inhibitor.
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 effects of age and sex 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 with young subjects, the AUCinf and T1/2 for LBQ657 were 42% and 30% greater, respectively, in elderly subjects. 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, respectively, in the elderly when compared with young subjects. All pharmacokinetic parameters of LCZ696 analytes (LBQ657 and valsartan) were similar between male and female subjects, indicating no effect on the pharmacokinetics of LCZ696 analytes based on sex. Considering the magnitude of change and its clinical significance, dose adjustment based on age or sex is not considered necessary.
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Langenickel
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
authors.forename: Jesika
authors.initials: J
authors.lastname: Petruck
authors.affiliation: Novartis Healthcare Pvt Ltd, Hyderabad, Telangana, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Kode
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Rajman
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Chandra
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Sam
authors.initials: S
authors.lastname: Rebello
authors.affiliation: Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
authors.forename: Gangadhar
authors.initials: G
authors.lastname: Sunkara
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000613:Aminobutyrates / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001713:Biphenyl Compounds / Q000097:blood; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors; D012737:Sex Factors; D013777:Tetrazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000068756:Valsartan / Q000097:blood; D055815:Young Adult
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; C000609743:LBQ657; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
keywords: LCZ696; age; angiotensin receptor neprilysin inhibitor; pharmacokinetics; sex