Journal Article Research Support, Non-U.S. Gov't Ppublish
PubMed: 38105420 DOI: 10.1111/cts.13701
No drug-drug interactions between selective prolyl-tRNA synthetase inhibitor, bersiporocin, and pirfenidone or nintedanib in healthy participants.
Clin Transl Sci 17(1):e13701
Authors: Wonsuk Shin, Min Young Park, Jongwoo Kim, Jihyeon Kim, Jun Hee Nam, Jongwon Choi, A-Young Yang, Hyounggyoon Yoo, Yil-Seob Lee, Anhye Kim
Affiliations
- Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea. CHA Global Clinical Trial Center, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea.
- Clinical Development Center, Daewoong Pharmaceutical Co. Ltd. Seoul, Republic of Korea.
- Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam-si, Gyeonggi-do, Republic of Korea. CHA Global Clinical Trial Center, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, Republic of Korea. Institute for Biomedical Informatics, CHA University School of Medicine, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
Abstract
Bersiporocin, a potent and selective prolyl-tRNA 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-label, two-part, one-sequence, three-period, three-treatment study was designed to evaluate the effect of drug-drug interactions (DDI) regarding their pharmacokinetics, safety, and tolerability in healthy participants. In addition, the pharmacokinetic profiles of the newly formulated, enteric-coated 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 mg, a single dose of bersiporocin 150 mg followed by multiple doses, and bersiporocin in combination with pirfenidone. In Part 2, participants were sequentially administered a single dose of nintedanib 150 mg, multiple doses of bersiporocin 150 mg, and bersiporocin in combination with nintedanib. Forty-six 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-tolerated. The newly formulated bersiporocin 150 mg 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.
MeSH
Ligases, Drug Interactions, Pharmacokinetics, Healthy Volunteers, Pharmaceutical Preparations, Therapeutics, Safety, Biomedical Research, Cytochrome P-450 Cyp2D6, Amino Acyl-Trna Synthetases, Rna, Transfer