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PK parameters and safety were assessed.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Study 1: esaxerenone peak plasma concentration (C<jats:sub>max<\/jats:sub>) and time to C<jats:sub>max<\/jats:sub> were unaltered by amlodipine coadministration, but mean half-life was slightly prolonged from 18.5 to 20.9\u2009h. Geometric least-squares mean (GLSM) ratios for C<jats:sub>max<\/jats:sub>, area under the plasma concentration\u2013time curve (AUC) from zero to last measurable concentration and from zero to infinity for esaxerenone + amlodipine versus esaxerenone were 0.958, 1.154, and 1.173, respectively. Study 2: corresponding GLSM ratios for amlodipine + esaxerenone versus amlodipine were 1.099, 1.185, and 1.214. Study 3: esaxerenone did not markedly alter digoxin PK. GLSM ratios for C<jats:sub>max<\/jats:sub>, trough plasma concentration, and AUC during a dosing interval for digoxin versus esaxerenone + digoxin were 1.130, 1.088, and 1.072, respectively.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>No drug\u2013drug interactions are expected during combination therapy with esaxerenone and either amlodipine or digoxin, based on a lack of any clinically relevant PK changes.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial registration<\/jats:title>\n<jats:p>Studies 1 and 2: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.jp\/cti-user\/trial\/ShowDirect.jsp?clinicalTrialId=26886\">JapicCTI-163379<\/jats:ext-link> (registered on 20 September 2016); Study 3: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.jp\/cti-user\/trial\/ShowDirect.jsp?clinicalTrialId=26938\">JapicCTI-163443<\/jats:ext-link> (registered on 24 November 2016).<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s40360-020-00423-4","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T08:07:53Z","timestamp":1596010073000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetic interactions of esaxerenone with amlodipine and digoxin in healthy Japanese subjects"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-0381","authenticated-orcid":false,"given":"Yoshiaki","family":"Kirigaya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanari","family":"Shiramoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Ishizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hinako","family":"Uchimaru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin","family":"Irie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Nakatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Ishizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"423_CR1","volume-title":"Global Health Observatory (GHO) data","author":"World Health Organization","year":"2019","unstructured":"World Health Organization. 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