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The pharmacogenetic (PG) effect of variants at the loci of organic cation transporter 1 (<jats:italic><jats:styled-content style=\"fixed-case\">OCT<\/jats:styled-content>1<\/jats:italic>) and UDP\u2010glucuronosyltransferase 2B7 (<jats:italic><jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>2B7<\/jats:italic>) on age\u2010dependent morphine clearance were evaluated in a cohort of critically ill neonatal patients using an opportunistic sampling design. Our primary results demonstrate the significant influence of <jats:styled-content style=\"fixed-case\">OCT<\/jats:styled-content>1 genotype (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and gestational age (<jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.005) on morphine PKs. A physiologically based pharmacokinetic (<jats:styled-content style=\"fixed-case\">PBPK<\/jats:styled-content>) model for morphine that accounted for <jats:styled-content style=\"fixed-case\">OCT<\/jats:styled-content>1 ontogeny and PG effect in post\u2010term neonates adequately described the clinically observed variability in morphine PKs. This study serves as a proof of concept for genotype\u2010dependent drug transporter ontogeny in neonates.<\/jats:p>","DOI":"10.1002\/cpt.1249","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T04:27:18Z","timestamp":1539145638000},"page":"761-768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Influence of <scp>OCT<\/scp>1 Ontogeny and Genetic Variation on Morphine Disposition in Critically Ill Neonates: Lessons From <scp>PBPK<\/scp> Modeling and Clinical Study"],"prefix":"10.1111","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9443-3402","authenticated-orcid":false,"given":"David","family":"Hahn","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8933-0254","authenticated-orcid":false,"given":"Chie","family":"Emoto","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-0598","authenticated-orcid":false,"given":"Joshua C.","family":"Euteneuer","sequence":"additional","affiliation":[{"name":"Division of Neonatology Perinatal Institute Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Division of Neonatology Children's Hospital &amp; Medical Center University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-9826","authenticated-orcid":false,"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Vinks","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0477-3102","authenticated-orcid":false,"given":"Tsuyoshi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,8]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-199310000-00007"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.108947"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0135-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-012-0006-9"},{"key":"e_1_2_9_5_1","first-page":"1","article-title":"Human UGT2B7 catalyzes morphine glucuronidation","volume":"25","author":"Coffman B.L.","year":"1997","journal-title":"Drug Metab. 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