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However, ibuprofen injection has not been approved for use in Chinese children. This study aimed to support its approval in this population using a model\u2010informed drug development (MIDD) approach. Ibuprofen injection (Fenliping\u00ae) received approval for Chinese pediatric indications in 2019, with a clinical trial waiver based on pediatric extrapolation using modeling and simulation. A physiologically based pharmacokinetic (PBPK) model was used to assess ethnic differences and determine the optimal dose for Chinese children. A single\u2010arm, open\u2010label trial was conducted in 40 pediatric patients aged 0.5\u20136\u2009years to confirm the appropriateness of the 10\u2009mg\/kg dose. Body temperature, pain scores, and adverse events were collected to evaluate efficacy, safety, tolerability, and were used as clinical endpoints for exposure\u2013response analysis. Sparse sampling was applied for pharmacokinetic analysis. A population pharmacokinetic (PopPK) model was developed using clinical data and used to refine the PBPK model and compare pharmacokinetics between Chinese and Caucasian children. Exposure\u2013response analysis evaluated the relationship between exposure and clinical outcomes. The PBPK model showed minimal ethnic impact on pharmacokinetics, supporting a 10\u2009mg\/kg dose. In febrile patients, 89.5% achieved temperature &lt;\u200938.5\u00b0C within 4\u2009hours. Pain scores decreased below threshold. One mild drug\u2010related adverse event occurred. PK parameters were comparable across ethnicities, and no exposure\u2013response relationship was observed. The MIDD approach supported full approval of ibuprofen injection in Chinese children. A 10\u2009mg\/kg dose was effective, safe, and well\u2010tolerated.<\/jats:p>","DOI":"10.1002\/cpt.70143","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T06:31:52Z","timestamp":1764138712000},"page":"729-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Model\u2010Informed Drug Development Supports Full Approval of Ibuprofen Injection in Chinese Pediatric Patients With Fever or Pain"],"prefix":"10.1002","volume":"119","author":[{"given":"Qianxi","family":"Lou","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Pediatric Drug Clinical Evaluation and R&amp;D Research Center of Engineering Technology, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; Shandong Provincial Qianfoshan Hospital, Shandong Pediatric Drug Clinical Evaluation and R&amp;D Research Center of Engineering Technology, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuokang","family":"Wang","sequence":"additional","affiliation":[{"name":"Chengdu Easton Biopharmaceuticals Co., Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Chengdu Easton Biopharmaceuticals Co., Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Bai","sequence":"additional","affiliation":[{"name":"Chengdu Easton Biopharmaceuticals Co., Ltd  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"van den Anker","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Clinical Pharmacology Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enmei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1830-338X","authenticated-orcid":false,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University &amp; 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Pharmacol."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70143","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70143","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70143","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T07:10:27Z","timestamp":1771312227000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":36,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/cpt.70143"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70143","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]},"assertion":[{"value":"2025-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}