{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:20:40Z","timestamp":1790371240002,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Saroglitazar magnesium, a dual PPAR \u03b1\/\u03b3 agonist, currently in Phase III for treating primary biliary cholangitis (PBC), was evaluated for its pharmacokinetic (PK) profile, safety, and pharmacodynamics in participants with cholestatic liver disease (CLD) across different levels of hepatic impairment (HI) and participants with severe renal impairment (RI). Three PK studies comparing saroglitazar with healthy controls were conducted: <jats:italic>Study 1<\/jats:italic> involved daily oral doses of 1 or 2\u2009mg for 4\u2009weeks in 12 PBC cirrhosis participants with mild or moderate HI; <jats:italic>Study 2<\/jats:italic> assessed single\u2010dose PK (2 or 4\u2009mg) in eight non\u2010cirrhotic CLD participants; <jats:italic>Study 3<\/jats:italic> evaluated single\u2010dose PK (2\u2009mg) in eight participants with severe RI. On day 1, saroglitazar exposure increased by 14.6\u201342% in mild HI vs. normal, but by day 28, levels were similar, indicating no accumulation. In moderate HI, exposure was significantly increased by 50.4\u201385% on days 1 and 28, with 34\u201346% lower clearance despite a similar half\u2010life. The moderate HI group had a 59% higher exposure than the non\u2010cirrhotic group. Saroglitazar (1 and 2\u2009mg) reduced alkaline phosphatase (ALP) levels by 17\u201340% after 4\u2009weeks in participants with abnormal baseline ALP. Single\u2010dose PK in non\u2010cirrhotic CLD (2 and 4\u2009mg) and severe RI (2\u2009mg) was comparable to matched controls without significant safety issues. Overall, saroglitazar (1 and 2\u2009mg) was safe and well\u2010tolerated in cholestatic cirrhosis with mild HI and participants with severe RI without major PK changes. Moderate HI increased exposure and decreased clearance without any safety concerns.<\/jats:p>","DOI":"10.1002\/cpt.3450","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T09:07:25Z","timestamp":1727860045000},"page":"240-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pharmacokinetic, Safety, and Pharmacodynamic Profiles of Saroglitazar Magnesium in Cholestatic Cirrhosis With Hepatic Impairment and Participants With Renal Impairment"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-1577","authenticated-orcid":false,"given":"Raj","family":"Vuppalanchi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-6559","authenticated-orcid":false,"given":"Taufik","family":"Momin","sequence":"additional","affiliation":[{"name":"Zydus Lifesciences Ltd.  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