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Lorundrostat, a highly selective inhibitor of CYP11B2, is a potential safe and effective treatment for aldosterone\u2010dependent, uncontrolled hypertension, including treatment\u2010resistant hypertension. Lorundrostat showed highly selective inhibition of CYP11B2 in\u00a0vitro, with 374\u2010fold selectivity for CYP11B2 vs. CYP11B1. A first\u2010in\u2010human study of single ascending doses ranging from 5 to 800\u2009mg and multiple ascending doses ranging from 40 to 360\u2009mg once daily was conducted in healthy participants. After single\u2010 and multiple\u2010dose administration, lorundrostat plasma levels peaked 1\u20133\u2009h after administration with a <jats:italic>t<\/jats:italic><jats:sub>1\/2<\/jats:sub> of 10\u201312\u2009h. Plasma aldosterone decreased up to 40% with single 100\u2010mg to 200\u2010mg doses and up to 70% with single 400 to 800\u2010mg doses. Plasma aldosterone returned to baseline within 16\u2009h after single 100\u2010mg doses and multiple once\u2010daily 120\u2010mg doses. Lorundrostat demonstrated a favorable safety profile in healthy participants. Dose\u2010 and exposure\u2010dependent inhibition of renal tubular sodium reabsorption was observed across a clinically relevant dose range with no suppression of basal or cosyntropin\u2010stimulated cortisol production and only a modest increase in mean serum potassium.<\/jats:p>","DOI":"10.1111\/cts.70000","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T03:39:24Z","timestamp":1723865964000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["First\u2010in\u2010human study evaluating safety, pharmacokinetics, and pharmacodynamics of lorundrostat, a novel and highly selective aldosterone synthase inhibitor"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4208-9790","authenticated-orcid":false,"given":"Hidetoshi","family":"Shimizu","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Group, Data Science Department, Ikuyaku, Integrated Value Development Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Tortorici","sequence":"additional","affiliation":[{"name":"Mineralys Therapeutics  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyasu","family":"Ohta","sequence":"additional","affiliation":[{"name":"Clinical Research &amp; Development II, Ikuyaku, Integrated Value Development Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Group, Data Science Department, Ikuyaku, Integrated Value Development Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheikh Mohammed Ashfaq","family":"Rahman","sequence":"additional","affiliation":[{"name":"Clinical Department Mitsubishi Tanabe Pharma Corporation  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Fujii","sequence":"additional","affiliation":[{"name":"Research Unit\/Neuroscience, Sohyaku, Innovative Research Division Mitsubishi Tanabe Pharma Corporation  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hiraga","sequence":"additional","affiliation":[{"name":"Translational Research, Sohyaku, Innovative Research Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizue","family":"Kawai","sequence":"additional","affiliation":[{"name":"Research Unit\/Immunology &amp; Inflammation, Sohyaku, Innovative Research Division Mitsubishi Tanabe Pharm Corporation  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanami","family":"Sugimoto\u2010Kawabata","sequence":"additional","affiliation":[{"name":"Sohyaku Strategy &amp; Planning Department, Sohyaku, Innovative Research Division Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattheus (Thijs)","family":"van Iersel","sequence":"additional","affiliation":[{"name":"ICON  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Jaap","family":"van Lier","sequence":"additional","affiliation":[{"name":"ICON  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Djedjos","sequence":"additional","affiliation":[{"name":"Mineralys Therapeutics  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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