{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:27:00Z","timestamp":1789928820705,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Osimertinib is a potent, highly selective, irreversible inhibitor of epidermal growth factor receptor (EGFR) and T790M resistance mutation. <jats:italic>In vitro<\/jats:italic> metabolism data suggested osimertinib is a substrate of cytochrome P450 (CYP)3A4\/5, a weak inducer of CYP3A, and an inhibitor of breast cancer resistance protein (BCRP). A combination of <jats:italic>in vitro<\/jats:italic> data, clinical pharmacokinetic data, and drug\u2010drug interaction (DDI) data of osimertinib in oncology patients were used to develop the physiologically based pharmacokinetic (PBPK) model and verify the DDI data of osimertinib. The model predicted the observed monotherapy concentration profile of osimertinib within 1.1\u2010fold, and showed good predictability (within 1.7\u2010fold) to the observed peak plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the curve (AUC) DDI ratio changes, when co\u2010administered with rifampicin, itraconazole, and simvastatin, but not with rosuvastatin. Based on observed clinical data and PBPK simulations, the recommended dose of osimertinib when dosed with strong CYP3A inducers is 160 mg once daily. PBPK modeling suggested no dose adjustment with moderate and weak CYP3A inducers.<\/jats:p>","DOI":"10.1002\/psp4.12289","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T09:36:44Z","timestamp":1519292204000},"page":"321-330","source":"Crossref","is-referenced-by-count":59,"title":["Development, Verification, and Prediction of Osimertinib Drug\u2013Drug Interactions Using PBPK Modeling Approach to Inform Drug Label"],"prefix":"10.1002","volume":"7","author":[{"given":"Venkatesh","family":"Pilla Reddy","sequence":"first","affiliation":[{"name":"Modelling and Simulation Oncology DMPK, IMED Biotech Unit AstraZeneca UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Walker","sequence":"additional","affiliation":[{"name":"Modelling and Simulation Oncology DMPK, IMED Biotech Unit AstraZeneca UK"},{"name":"Certara QSP, Simcyp Ltd Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Sharma","sequence":"additional","affiliation":[{"name":"Safety and ADME Translational Sciences Drug Safety and Metabolism, IMED Biotech Unit AstraZeneca UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ballard","sequence":"additional","affiliation":[{"name":"DMPK, Oncology IMED Biotech Unit AstraZeneca UK"},{"name":"DMPK Consulting High Peak UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6555-8131","authenticated-orcid":false,"given":"Karthick","family":"Vishwanathan","sequence":"additional","affiliation":[{"name":"QCP, Early Clinical Development IMED Biotech Unit AstraZeneca USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"e_1_2_13_1_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-0337"},{"key":"e_1_2_13_2_1","unstructured":"US FDA AstraZeneca Pharmaceuticals LP TAGRISSOTM(osimertinib) tablet: highlights of prescribing information. <https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/208065s007lbl.pdf> (2017). January 29 2018."},{"key":"e_1_2_13_3_1","unstructured":"TAGRISSO (osimertinib) \u2010 EMA \u2010 Europa.eu. <http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/004124\/human_med_001961.jsp&mid=WC0b01ac058001d124>. February 11 2017."},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-2992-z"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.069203"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1830"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13223"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250802691074"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9210-3"},{"key":"e_1_2_13_10_1","unstructured":"Guidance for Industry: Drug Interaction Studies \u2010 Study Design Data Analysis Implications for Dosing and Labelling Recommendations. <https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm292362.pdf>. February2012."},{"key":"e_1_2_13_11_1","unstructured":"Guideline on the Investigation of Drug Interactions (CPMP\/EWP\/560\/95\/Rev. 1 Corr.*) <http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/07\/WC500129606.pdf>.2012."},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13534"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.34.15_suppl.e14098"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010387792"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-008-0571-5"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.035071"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.4.778"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1995.tb00001.x"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12377"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6663"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0330-y"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.988"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.145"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.128"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.917"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0097-y"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1411817"}],"updated-by":[{"DOI":"10.1002\/psp4.12386","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2019,2,17]],"date-time":"2019-02-17T00:00:00Z","timestamp":1550361600000}}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpsp4.12289","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.12289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T21:26:57Z","timestamp":1694726817000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.12289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":27,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/psp4.12289"],"URL":"https:\/\/doi.org\/10.1002\/psp4.12289","archive":["Portico"],"relation":{"erratum":[{"id-type":"doi","id":"10.1002\/psp4.12386","asserted-by":"object"}]},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,15]]}}}