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The pharmacokinetics (PK) of nilotinib in specific populations such as pregnant and lactating people remain poorly understood. Therefore, the objectives of the current study were to develop a physiologically based pharmacokinetic (PBPK) model to predict nilotinib PK in virtual drug\u2010drug interaction (DDI) studies, as well as in pediatric, pregnant, and lactating populations. The nilotinib PBPK model was built in PK\u2010Sim, which is part of the free and open\u2010source software Open Systems Pharmacology. The observed clinical data for the validation of the nilotinib models were obtained from the literature. The model reasonably predicted nilotinib concentrations in the adult population; the DDIs between nilotinib and rifampin or ketoconazole in the adult population; and the PK in the pediatric, pregnant, and lactating populations, although in the latter 2 populations plasma concentrations were slightly underestimated. The ratio of predicted versus observed PK parameters for the adult model ranged from 0.71 to 1.11 for area under the concentration\u2010time curve and 0.55 to 0.95 for maximum concentration. For the DDI, the predicted area under the concentration\u2010time curve ratio and maximum concentration ratio fell within the Guest criterion. The current study demonstrated the utility of using PBPK modeling to understand the mechanistic basis of PK differences between adults and specific populations, such as pediatrics, and pregnant and lactating individuals, indicating that this technology can potentially inform or optimize dosing conditions in specific populations.<\/jats:p>","DOI":"10.1002\/jcph.2379","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:04:29Z","timestamp":1698843869000},"page":"323-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Physiologically Based Pharmacokinetic Modeling of Nilotinib for Drug\u2010Drug Interactions, Pediatric Patients, and Pregnancy and Lactation"],"prefix":"10.1002","volume":"64","author":[{"given":"Xiaomei I.","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Children's National Hospital  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby","family":"Leong","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology US Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2005-9301","authenticated-orcid":false,"given":"Gilbert J.","family":"Burckart","sequence":"additional","affiliation":[{"name":"Office of Clinical Pharmacology US Food and Drug Administration  Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1108-5719","authenticated-orcid":false,"given":"Andr\u00e9","family":"Dallmann","sequence":"additional","affiliation":[{"name":"Bayer HealthCare SAS, Loos, France, on behalf of: Pharmacometrics\/Modeling and Simulation, Research and Development, Pharmaceuticals, Bayer AG  Leverkusen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"US Food and Drug Administration: TASIGNA (nilotinib) capsules: Revised 9\/2021. 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