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The most relevant prerequisite for reliable PBPK\u2010based translation of adult pharmacokinetics of a small molecule to children is knowledge of the drug\u2010specific absorption, distribution, metabolism, and elimination (ADME) processes in adults together with existing information about ontogeny of ADME processes relevant for the drug. All mechanisms driving a drug's clearance are of specific importance. For other drug modalities, our knowledge of ADME processes and ontogeny is still limited. More research is required, for example, to understand why some therapeutic proteins show complex differences in pharmacokinetics between adults and children, whereas other proteins seem to follow simple allometric scaling rules. Ontogeny information originates from various sources, such as (semi)quantitative mRNA expression, in vitro activity data, and deconvolution of in vivo pharmacokinetic data. The workflow for pediatric predictions is well described in several articles documenting successful translation from adults to children. The technical hurdles for PBPK modeling are low. State\u2010of\u2010the\u2010art PBPK modeling software tools provide integrated pediatric translation workflows. For example, PK\u2010Sim and MoBi are freely available as fully transparent open\u2010source software via Open Systems Pharmacology (OSP). With the latest 2019 software release, version 8.0, OSP even provides a fully integrated technical framework for the qualification (and requalification) of any specific intended PBPK use in line with Food and Drug Administration and European Medicines Agency PBPK guidance. Qualification packages for pediatric translation are available on the OSP platform.<\/jats:p>","DOI":"10.1002\/jcph.1497","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T09:32:46Z","timestamp":1568107966000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Predictive Pediatric Modeling and Simulation Using Ontogeny Information"],"prefix":"10.1002","volume":"59","author":[{"given":"Ibrahim","family":"Ince","sequence":"first","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Solodenko","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Frechen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Dallmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Niederalt","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Schlender","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Burghaus","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Lippert","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Willmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Research &amp; Development, Pharmaceuticals Bayer AG  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612821666150901110533"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645100-00005"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1084"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0422-3"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.622"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2018.10.033"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.33"},{"key":"e_1_2_5_9_1","unstructured":"FDA.Pediatric study plans: content of and process for submitting initial pediatric study plans and amended pediatric study plans.https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/pediatric-study-plans-content-and-process-submitting-initial-pediatric-study-plans-and-amended. 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