{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T12:40:29Z","timestamp":1763728829603,"version":"3.40.5"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A novel dual PI3K \u03b1\/\u03b4 inhibitor, TQ\u2010B3525, has been developed for the targeted treatment of lymphoma and solid tumors. TQ\u2010B3525 is primarily metabolized by CYP3A4 and FOM3, while also serving as a substrate for the P\u2010glycoprotein transporter. The aim of this study was to anticipate the drug\u2013drug interaction (DDI) of TQ\u2010B3525 and its two metabolites with CYP3A4 enzyme potent inducer (rifampicin) and CYP3A4\/P\u2010gp inhibitor (itraconazole) utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Clinical data from healthy and cancer patient adults were employed to construct and evaluate the PBPK model for TQ\u2010B3525, M3, and M8\u20103. Models involving rifampicin combined with midazolam, itraconazole combined with midazolam or digoxin were utilized to showcase the robustness of evaluating DDI effects. The simulated drug exposure of TQ\u2010B3525, M3, and M8\u20103 in healthy and patient adults were consistent with clinical data, and the mean fold error values were within the acceptable ranges. The simulated results of positive substrates correspond to those reported in the literature. Co\u2010administration with rifampicin reduces C<jats:sub>max<\/jats:sub> and AUC of TQ\u2010B3525 to 76.1% and 46.0%, while increasing the levels of M3 and M8\u20103. With itraconazole, C<jats:sub>max<\/jats:sub> and AUC of TQ\u2010B3525 rise to 131% and 204%, but decrease substantially for M3 and M8\u20103. PBPK model simulation results showed that the systemic exposure of TQ\u2010B3525 was significantly affected when co\u2010administered with CYP3A4\/P\u2010gp inducers and inhibitors. This indicates that the combination with strong inducers and inhibitors should be carefully avoided or adjust the dosage of TQ\u2010B3525 in clinic.<\/jats:p>","DOI":"10.1002\/jcph.6111","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T11:55:24Z","timestamp":1722945324000},"page":"1517-1527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Predict the Drug\u2013Drug Interaction of a Novel PI3K\u03b1\/\u03b4 Inhibitor, TQ\u2010B3525, and Its Two Metabolites Using Physiologically Based Pharmacokinetic Modeling"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5626-6574","authenticated-orcid":false,"given":"Shixing","family":"Zhu","sequence":"first","affiliation":[{"name":"Clinical Medicine Department Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding","family":"Yu","sequence":"additional","affiliation":[{"name":"Clinical Medicine Department Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Medicine Department Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3561-3160","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Medicine Department Chia Tai Tianqing Pharmaceutical Group Co., Ltd. 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