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We aimed to apply physiologically based pharmacokinetic (PBPK) modeling to investigate the dose adjustment strategy for tacrolimus during short\u2010term coadministration with ritonavir. PBPK models for tacrolimus and ritonavir were successfully developed based on in vitro and clinical data, and were used to predict drug\u2010drug interaction levels via metabolic enzyme inhibition mechanisms. The recommended dose strategy based on our model simulation is to hold tacrolimus during nirmatrelvir\/ritonavir treatment and restart half of the initial dose on day 3 after the 5\u2010day ritonavir course, followed by resuming the full dose on day 5. This administration strategy can maintain trough concentrations of tacrolimus within the therapeutic window during and after ritonavir treatment.<\/jats:p>","DOI":"10.1002\/cpdd.1572","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:24:47Z","timestamp":1752240287000},"page":"797-808","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Physiologically Based Pharmacokinetic Modeling to Evaluate Drug\u2010Drug Interactions of Tacrolimus With Ritonavir, a CYP3A Irreversible Inhibitor: Applications for Dosing Optimization in Transplant Patients"],"prefix":"10.1002","volume":"14","author":[{"given":"Yanjun","family":"Jiang","sequence":"first","affiliation":[{"name":"Phase I Clinical Trial Unit The First Affiliated Hospital With Nanjing Medical University  Nanjing China"},{"name":"Department of Clinical Pharmacology School of Pharmacy College Nanjing Medical University  Nanjing 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