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Pharmacokinetic drug–drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel‐ethinyl estradiol in healthy subjects
Author(s) -
Gan Lu,
Jiang Xuemin,
Mendonza Anisha,
Swan Therese,
Reynolds Christine,
Nguyen Joanne,
Pal Parasar,
Neelakantham Srikanth,
Dahlke Marion,
Langenickel Thomas,
Rajman Iris,
Akahori Mizuki,
Zhou Wei,
Rebello Sam,
Sunkara Gangadhar
Publication year - 2015
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.181
Subject(s) - cmax , levonorgestrel , pharmacokinetics , pharmacology , medicine , omeprazole , sacubitril, valsartan , cmin , sacubitril , drug interaction , valsartan , dipeptidyl peptidase 4 inhibitor , endocrinology , population , diabetes mellitus , type 2 diabetes , environmental health , family planning , blood pressure , research methodology
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 AUC inf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the C max of sacubitril, and 11% and 13% decreases in AUC inf and C max of valsartan were observed. Co‐administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUC tau,ss and C max,ss of metformin were decreased by 23%. Co‐administration of LCZ696 with levonorgestrel‐ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUC inf of levonorgestrel. The C max of levonorgestrel decreased by 15%, and AUC tau,ss and C max,ss of valsartan decreased by 14% and 16%, respectively. Co‐administration of LCZ696 with omeprazole, metformin, or levonorgestrel‐ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions.