{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:50:42Z","timestamp":1789537842332,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Apararenone is a long\u2010acting, nonsteroidal mineralocorticoid receptor antagonist (MRA). The safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of single\u2010 and multiple\u2010dose apararenone were assessed in 3 phase 1 randomized, double\u2010blind studies in 223 healthy adults. Study 1 assessed the PK, safety\/tolerability, and PD of single\u2010dose apararenone (3.75\u2013640 mg) and multiple\u2010dose apararenone (10\u201340 mg\/day on days 1\u201314, 320 mg loading dose on day 1 + 10 mg\/day on days 2\u201314, or 40\u2013320 mg loading dose on day 1 + 2.5\u201320 mg\/day on days 2\u201314) in Caucasian and Black men and women. Study 2 assessed the PK and safety of single\u2010dose apararenone (5\u2013320 mg) in healthy Japanese men. Study 3 assessed the PK, PD, and safety\/tolerability of single\u2010dose apararenone (160 or 640 mg) or eplerenone (200 mg; only for 160 mg of apararenone), each after fludrocortisone challenge in Caucasian men. In studies 1 and 2, an approximately dose\u2010proportional increase was observed in PK parameters over the apararenone dose range of 3.75\u201340 mg; at higher doses, a less than dose\u2010proportional increase was observed. Food, sex, age, and race had no apparent effect on apararenone PK. A long half\u2010life was seen for apararenone and its principal metabolite; in addition, the exposure of the metabolite was lower than that of apararenone. Apararenone suppressed the decrease in urinary sodium and potassium ion ratio that occurs after loading with fludrocortisone. These studies support the mechanism of action of apararenone as an MRA, and further clinical development is warranted.<\/jats:p>","DOI":"10.1002\/cpdd.855","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T04:21:12Z","timestamp":1597983672000},"page":"353-365","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Phase 1 Studies to Define the Safety, Tolerability, and Pharmacokinetic and Pharmacodynamic Profiles of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone in Healthy Volunteers"],"prefix":"10.1002","volume":"10","author":[{"given":"Tadakatsu","family":"Nakamura","sequence":"first","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiro","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Corporation  Tokyo 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