{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T12:20:25Z","timestamp":1753878025254,"version":"3.41.2"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bersiporocin, a potent and selective prolyl\u2010tRNA synthetase inhibitor, is expected to show a synergistic effect with pirfenidone or nintedanib in patients with idiopathic pulmonary fibrosis. To validate the combination therapy of bersiporocin with pirfenidone or nintedanib, a randomized, open\u2010label, two\u2010part, one\u2010sequence, three\u2010period, three\u2010treatment study was designed to evaluate the effect of drug\u2013drug interactions (DDI) regarding their pharmacokinetics, safety, and tolerability in healthy participants. In addition, the pharmacokinetic profiles of the newly formulated, enteric\u2010coated bersiporocin tablet were evaluated after single and multiple administrations. The potential effects of cytochrome P450 2D6 (CYP2D6) genotyping on bersiporocin pharmacokinetics and DDI were also explored. In Part 1, participants were sequentially administered a single dose of pirfenidone 600\u2009mg, a single dose of bersiporocin 150\u2009mg followed by multiple doses, and bersiporocin in combination with pirfenidone. In Part 2, participants were sequentially administered a single dose of nintedanib 150\u2009mg, multiple doses of bersiporocin 150\u2009mg, and bersiporocin in combination with nintedanib. Forty\u2010six participants completed the study. There was no significant pharmacokinetic DDI between bersiporocin, and pirfenidone or nintedanib. All adverse events (AEs) were mild to moderate and did not include serious AEs, suggesting bersiporocin alone or in combination therapy were well\u2010tolerated. The newly formulated bersiporocin 150\u2009mg tablet showed a moderate accumulation index. There was no significant difference in the pharmacokinetic profiles after administration of bersiporocin alone or in combination therapy between CYP2D6 phenotypes. In conclusion, there are no significant DDI regarding the pharmacokinetics, safety, and tolerability of bersiporocin administration with pirfenidone or nintedanib.<\/jats:p>","DOI":"10.1111\/cts.13701","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T04:00:08Z","timestamp":1702872008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["No drug\u2013drug interactions between selective prolyl\u2010tRNA synthetase inhibitor, bersiporocin, and pirfenidone or nintedanib in healthy participants"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-5726","authenticated-orcid":false,"given":"Wonsuk","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center CHA University School of Medicine  Seongnam\u2010si Gyeonggi\u2010do Republic of Korea"},{"name":"CHA Global Clinical Trial Center, CHA Bundang Medical Center  Seongnam\u2010si Gyeonggi\u2010do Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Young","family":"Park","sequence":"additional","affiliation":[{"name":"Clinical Development Center, Daewoong Pharmaceutical Co., Ltd.  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jongwoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinical Development Center, Daewoong Pharmaceutical Co., Ltd.  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Clinical Development Center, Daewoong Pharmaceutical Co., Ltd.  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Hee","family":"Nam","sequence":"additional","affiliation":[{"name":"Clinical Development Center, Daewoong Pharmaceutical Co., Ltd.  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jongwon","family":"Choi","sequence":"additional","affiliation":[{"name":"Clinical Development Center, Daewoong Pharmaceutical Co., Ltd.  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