{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T14:48:33Z","timestamp":1767192513563},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Omecamtiv mecarbil (OM), a novel cardiac myosin activator, is being evaluated for the treatment of heart failure with reduced ejection fraction. In vitro studies demonstrate OM as a substrate and inhibitor of P\u2010glycoprotein (P\u2010gp), which can result in drug\u2010drug interactions. Two phase 1, open\u2010label studies assessed the effect of coadministration of OM (50\u2010mg single dose) on the pharmacokinetics of digoxin (0.5\u2010mg single dose; N = 15), a P\u2010gp substrate, and the effect of coadministration of amiodarone (600\u2010mg single dose), a P\u2010gp inhibitor, on the pharmacokinetics of OM (50\u2010mg single dose; N = 14) in healthy subjects. The ratios of the geometric least squares mean (90% confidence interval [CI]) of digoxin coadministered with OM vs digoxin alone for area under the plasma concentration\u2013time curve (AUC) from time 0 to infinity, AUC from time 0 to the time of the last quantifiable concentration, and maximum observed plasma concentration were 1.06 (90%CI, 0.99\u20101.14), 1.06 (90%CI, 0.98\u20101.14), and 1.08 (90%CI, 0.92\u20101.26), respectively. The ratios of the geometric least squares mean of OM coadministered with amiodarone vs OM alone for AUC from time 0 to infinity, AUC from time 0 to the time of the last quantifiable concentration, and maximum observed plasma concentration were 1.21 (90%CI, 1.08\u20101.36), 1.21 (90%CI, 1.07\u20101.36), and 1.08 (90%CI, 0.96\u20101.22), respectively. In conclusion, OM coadministered with digoxin or amiodarone did not result in any clinically relevant pharmacokinetic drug\u2010drug interactions.<\/jats:p>","DOI":"10.1002\/cpdd.1028","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T18:59:56Z","timestamp":1633978796000},"page":"388-396","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacokinetic Drug\u2010Drug Interaction Study of Omecamtiv Mecarbil With Amiodarone and Digoxin in Healthy Subjects"],"prefix":"10.1002","volume":"11","author":[{"given":"Ashit","family":"Trivedi","sequence":"first","affiliation":[{"name":"Amgen Inc  Thousand Oaks California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Winnie","family":"Sohn","sequence":"additional","affiliation":[{"name":"Amgen Inc  Thousand Oaks California 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