{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:42:13Z","timestamp":1784612533413,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pediatric physiologically\u2010based modeling in drug development has grown in the past decade and optimizing the underlying systems parameters is important in relation to overall performance. In this study, variation of clinical oral bioavailability of midazolam as a function of age is used to assess the underlying ontogeny models for intestinal CYP3A4. Data on midazolam bioavailability in adults and children and different ontogeny patterns for intestinal CYP3A4 were first collected from the literature. A pediatric PBPK model was then used to assess six different ontogeny models in predicting bioavailability from preterm neonates to adults. The average fold error ranged from 0.7 to 1.38, with the rank order of least to most biased model being No Ontogeny\u2009&lt;\u2009Upreti\u2009=\u2009Johnson\u2009&lt;\u2009Goelen\u2009&lt;\u2009Chen\u2009&lt;\u2009Kiss. The absolute average fold error ranged from 1.17 to 1.64 with the rank order of most to least precise being Johnson\u2009&gt;\u2009Upreti\u2009&gt;\u2009No Ontogeny\u2009&gt;\u2009Goelen\u2009&gt;\u2009Kiss\u2009&gt;\u2009Chen. The optimal ontogeny model is difficult to discern when considering the possible influence of CYP3A5 and other population variability; however, this study suggests that from term neonates and older a faster onset Johnson model with a lower fraction at birth may be close to this. For inclusion in other PBPK models, independent verification will be needed to confirm these results. Further research is needed in this area both in terms of age\u2010related changes in midazolam and similar drug bioavailability and intestinal CYP3A4 ontogeny.<\/jats:p>","DOI":"10.1002\/psp4.13192","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T09:31:35Z","timestamp":1719394295000},"page":"1570-1581","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Combining data on the bioavailability of midazolam and physiologically\u2010based pharmacokinetic modeling to investigate intestinal <scp>CYP3A4<\/scp> ontogeny"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0778-0081","authenticated-orcid":false,"given":"Trevor N.","family":"Johnson","sequence":"first","affiliation":[{"name":"Certara UK Limited  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8729-9951","authenticated-orcid":false,"given":"Hannah K.","family":"Batchelor","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6796-3210","authenticated-orcid":false,"given":"Jan","family":"Goelen","sequence":"additional","affiliation":[{"name":"Centre for Neonatal and Paediatric Infection, Antimicrobial Resistance Research Group, St George's University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-9236","authenticated-orcid":false,"given":"Richard D.","family":"Horniblow","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, College of Medical and Dental Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3255-8925","authenticated-orcid":false,"given":"Jean","family":"Dinh","sequence":"additional","affiliation":[{"name":"Certara UK Limited  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12764"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"S160","article-title":"Application of PBPK Modeling and simulation for regulatory decision making and its impact on US prescribing information: an update on the 2018\u20132019 submissions to the US FDA's Office of Clinical Pharmacology","volume":"60","author":"Zhang X","year":"2020","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107541"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.20519"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0576-7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12306"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-9896-z"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.068643"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113156"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37149-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90162-9b"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-9556(25)08440-5"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2015.02.007"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.005611"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2001.01370.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2023.08.011"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.121.000559"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/86882"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.123.001270"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph2452"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.585"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0140-7"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15092231"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.054841"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2004.10.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2018.01.009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2002.01223.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12295"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00825-6"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.2165\/11318160-000000000-00000"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-020-09684-2"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100237"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01257-z"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00679782"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122012832"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1890"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201510-2114OC"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-018-2458-6"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.10.008"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2024.123962"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15112579"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9099-y"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2019.01.028"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2384"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.905"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2134"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645090-00005"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T18:35:23Z","timestamp":1744310123000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/psp4.13192"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13192","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]},"assertion":[{"value":"2024-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}