{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:37:05Z","timestamp":1790235425502,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>The accuracy of physiologically based pharmacokinetic (PBPK) model prediction in children, especially those younger than 2 years old, has not been systematically evaluated. The aim of this study was to characterize the pediatric predictive performance of the PBPK approach for 10 drugs extensively metabolized by CYP1A2 (theophylline), CYP2C8 (desloratidine, montelukast), CYP2C9 (diclofenac), CYP2C19 (esomeprazole, lansoprazole), CYP2D6 (tramadol), and CYP3A4 (itraconazole, ondansetron, sufentanil). Model performance in children was evaluated by comparing simulated plasma concentration\u2013time profiles with observed clinical results for each drug and age group. PBPK models reasonably predicted the pharmacokinetics of desloratadine, diclofenac, itraconazole, lansoprazole, montelukast, ondansetron, sufentanil, theophylline, and tramadol across all age groups. Collectively, 58 out of 67 predictions were within 2\u2010fold and 43 out of 67 predictions within 1.5\u2010fold of observed values. Developed PBPK models can reasonably predict exposure in children age 1 month and older for an array of predominantly CYP metabolized drugs.<\/jats:p>","DOI":"10.1002\/cpt.905","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T02:46:43Z","timestamp":1507862803000},"page":"188-200","source":"Crossref","is-referenced-by-count":74,"title":["Predictive Performance of Physiologically Based Pharmacokinetic (PBPK) Modeling of Drugs Extensively Metabolized by Major Cytochrome P450s in Children"],"prefix":"10.1111","volume":"104","author":[{"given":"Wangda","family":"Zhou","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor N.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Simcyp (A Certara Company) Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khanh H.","family":"Bui","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.Y. Amy","family":"Cheung","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Li","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Xu","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidal","family":"Al\u2010Huniti","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diansong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology AstraZeneca Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.169"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.1899"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2014.45"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645090-00005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2012.12"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.55"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.19"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.33"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","DOI":"10.1002\/psp4.12101","article-title":"Predictive performance of physiologically based pharmacokinetic and population pharmacokinetic modeling of renally cleared drugs in children","author":"Zhou W.","year":"2016","journal-title":"CPT Pharmacometrics Syst. Pharmacol."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx700079z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000794"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.011411"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.41"},{"key":"e_1_2_9_14_1","article-title":"Physiologically based pharmacokinetic modeling to predict drug\u2010drug interactions with efavirenz involving simultaneous inducing and inhibitory effects on cytochromes","author":"Marzolini C.","year":"2016","journal-title":"Clin. Pharmacokinet."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12070"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.30"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/15287390490273550"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645100-00005"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.585"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.041293"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.30.8.883"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199302000-00008"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200304000-00011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.013359"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.067595"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-013-0012-x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-1293-z"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.237"},{"key":"e_1_2_9_29_1","unstructured":"Mulugeta L.What do we look for to support pediatric dosing?<https:\/\/wwwfdagov\/downloads\/newsevents\/meetingsconferencesworkshops\/ucm415211pdf>. Accessed 6 September2015)."},{"key":"e_1_2_9_30_1","unstructured":"Pediatric studies conducted under FDAAA. <http:\/\/wwwfdagov\/Drugs\/DevelopmentApprovalProcess\/DevelopmentResources\/UCM049872>. Accessed 28 October2015)."},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.520"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250600683197"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00493567"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250802691074"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.062620"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241001-00006"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011035007591"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.037689"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/S0090-9556(25)06820-5","article-title":"Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans","volume":"23","author":"Dixon C.M.","year":"1995","journal-title":"Drug Metab. Dispos."},{"key":"e_1_2_9_40_1","unstructured":"Zofran FDA label. <http:\/\/wwwaccessdatafdagov\/drugsatfda_docs\/label\/2010\/020007s040 020403s018lblpdf>. Accessed 6 September2016."},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70130-X"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0352-5"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-015-9803-z"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.10005"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20073"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20322"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20502"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9210-3"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0140-7"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-310148.43"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.905","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.905","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T09:15:03Z","timestamp":1750929303000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,20]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1002\/cpt.905"],"URL":"https:\/\/doi.org\/10.1002\/cpt.905","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,20]]}}}