{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:12:38Z","timestamp":1788502358391,"version":"build-2803163510"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Senaparib (Sepalna\u00ae), a novel oral poly (adenosine diphosphate -ribose) polymerase (PARP) 1\/2 inhibitor, was approved in China in 2025 as maintenance therapy for advanced ovarian cancer. The recommended starting dose is 100\u00a0mg once daily, which may be adjusted to 80\u00a0mg, 60\u00a0mg, or 40\u00a0mg to manage adverse events. While conventional bioequivalence (BE) clinical studies established equivalence between the 10\u00a0mg and 20\u00a0mg capsules strengths at the 100\u00a0mg dose level, these findings cannot be extrapolated to the lower dose range due to senaparib\u2019s nonlinear pharmacokinetics and the current absence of definitive regulatory guidance for such scenarios. This study aimed to evaluate the bioequivalence between the 10\u00a0mg and 20\u00a0mg capsule strengths of senaparib, a drug exhibiting nonlinear pharmacokinetics, across the 20\u201380\u00a0mg dose range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed and validated an integrated approach combining physiologically based pharmacokinetic (PBPK) modeling with\n                      <jats:italic>in vitro<\/jats:italic>\n                      dissolution data to evaluate virtual bioequivalence (VBE) between the two capsule strengths across the 20\u201380\u00a0mg dose range.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Under all evaluated conditions including variations in sample size, intra-individual variability levels, and prandial states (fasted and fed), the geometric mean ratios (GMRs) of key pharmacokinetic (PK) parameters consistently approached 100%, thereby confirming bioequivalence across the specified dosing range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This PBPK-VBE framework provides supportive evidence for bioequivalence bridging of senaparib capsule strengths across the linear dose range, illustrating the potential utility of this approach for formulation bridging when direct clinical BE studies across all dose levels are impractical.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1918344","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:29:36Z","timestamp":1788499776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A PBPK-VBE approach for bioequivalence extrapolation of senaparib capsule strengths in the context of nonlinear pharmacokinetics: bridging from the clinical starting dose to the linear pharmacokinetic range"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaofei","family":"Wu","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation Innovative Drugs for Major Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation Innovative Drugs for Major Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Impact Therapeutics Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd.","place":["Shanghai, China"]},{"name":"School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[{"name":"Shanghai Impact Therapeutics Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suixiong","family":"Cai","sequence":"additional","affiliation":[{"name":"Shanghai Impact Therapeutics Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Impact Therapeutics Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Impact Therapeutics Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Impact Therapeutics Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing Key Laboratory of Key Technologies for Early Clinical Trial Evaluation Innovative Drugs for Major Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.3390\/pharmaceutics16111414","article-title":"Advancements in virtual bioequivalence: a systematic reviewof computational methods and regulatory perspectives in the pharmaceutical industry","volume":"16","author":"Alotaiq","year":"2024","journal-title":"Pharmaceutics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1208\/s12248-021-00672-z","article-title":"Proof of concept in assignment of within-subject variability during virtual bioequivalence studies: propagation of intra-subject variation in gastrointestinal physiology using physiologically based pharmacokinetic modeling","volume":"24","author":"Bego","year":"2022","journal-title":"AAPS Journal"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1158\/1538-7445.am2022-1399","article-title":"Discovery and development of PARP inhibitor senaparib","volume":"82","author":"Cai","year":"2022","journal-title":"Cancer Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1158\/1535-7163.MCT-23-0625","article-title":"The discovery of a potent PARP1 inhibitor senaparib","volume":"24","author":"Cai","year":"2025","journal-title":"Mol. Cancer Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e1259","DOI":"10.1093\/oncolo\/oyad163","article-title":"Safety, tolerability, and pharmacokinetics of senaparib, a novel PARP1\/2 inhibitor, in Chinese patients with advanced solid tumors: a phase I trial","volume":"28","author":"Cao","year":"2023","journal-title":"Oncol."},{"key":"B6","first-page":"235","volume-title":"Pharmacopoeia of the People's Republic of China","year":"2020"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1002\/cncr.34662","article-title":"A phase 1 dose-escalation study of the poly (ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors","volume":"129","author":"Gao","year":"2023","journal-title":"Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1208\/s12248-019-0298-x","article-title":"Dissolution and translational modeling strategies toward establishing an in vitro-in vivo link-a workshop summary report","volume":"21","author":"Heimbach","year":"2019","journal-title":"AAPS Journal"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1111\/bcp.15624","article-title":"Effect of a strong CYP3A4 inhibitor and inducer on the pharmacokinetics of senaparib (IMP4297) in healthy volunteers: a drug-drug interaction study","volume":"89","author":"Hu","year":"2023","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B10","volume-title":"Senaparib Capsules (Sepalna\u00ae). Chinese Prescribing Information","year":"2025"},{"key":"B11","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1208\/s12248-023-00831-4","article-title":"Modelling based approaches to support generic drug regulatory submissions-practical considerations and case studies","volume":"25","author":"Karnati","year":"2023","journal-title":"AAPS Journal"},{"key":"B12","doi-asserted-by":"publisher","first-page":"876","DOI":"10.3390\/ph17070876","article-title":"Advancing virtual bioequivalence for orally administered drug products: methodology, real-world applications and future outlook","volume":"17","author":"Kollipara","year":"2024","journal-title":"Pharmaceuticals"},{"key":"B13","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1208\/s12248-015-9849-y","article-title":"Deconvolution and IVIVC: exploring the role of rate-limiting conditions","volume":"18","author":"Margolskee","year":"2016","journal-title":"AAPS Journal"},{"key":"B14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1208\/s12248-023-00794-6","article-title":"Virtual bioequivalence assessment of elagolix formulations using physiologically based pharmacokinetic modeling","volume":"25","author":"Mukherjee","year":"2023","journal-title":"AAPS Journal"},{"key":"B15","volume-title":"The National Medical Products Administration Approved the Marketing of Senaparib Capsules","year":"2025"},{"key":"B16","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1208\/s12248-018-0252-3","article-title":"Applications of clinically relevant dissolution testing: workshop summary report","volume":"20","author":"Suarez-Sharp","year":"2018","journal-title":"AAPS Journal"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1038\/s41591-024-03003-9","article-title":"Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial","volume":"30","author":"Wu","year":"2024","journal-title":"Nat. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"105618","DOI":"10.1016\/j.ejps.2020.105618","article-title":"In silico prediction of bioequivalence of isosorbide mononitrate tablets with different dissolution profiles using PBPK modeling and simulation","volume":"157","author":"Zhang","year":"2021","journal-title":"Eur. J. Pharm. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1021\/acs.molpharmaceut.2c00688","article-title":"Predicting the pharmacokinetics of orally administered drugs across BCS classes 1-4 by virtual bioequivalence model","volume":"20","author":"Zhang","year":"2023","journal-title":"Mol. Pharm."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1918344\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:29:38Z","timestamp":1788499778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1918344\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":19,"alternative-id":["10.3389\/fphar.2026.1918344"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1918344","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]},"article-number":"1918344"}}