{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:26:45Z","timestamp":1785306405519,"version":"3.55.0"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T00:00:00Z","timestamp":1721520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5R01HD097775"],"award-info":[{"award-number":["5R01HD097775"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"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>Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device commonly used to treat cardiac arrest in children. The American Heart Association guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care recommend using amiodarone as a first\u2010line agent to treat ventricular arrhythmias in children with cardiac arrest. However, there are no dosing recommendations for amiodarone to treat ventricular arrhythmias in pediatric patients on ECMO. Amiodarone has a high propensity for adsorption to the ECMO components due to its physicochemical properties leading to altered pharmacokinetics (PK) in ECMO patients. The change in amiodarone PK due to interaction with ECMO components may result in a difference in optimal dosing in patients on ECMO when compared with non\u2010ECMO patients. To address this clinical knowledge gap, a physiologically\u2010based pharmacokinetic model of amiodarone was developed in adults and scaled to children, followed by the addition of an ECMO compartment. The pediatric model included ontogeny functions of cytochrome P450 (CYP450) enzyme maturation across various age groups. The ECMO compartment was parameterized using the adsorption data of amiodarone obtained from ex\u00a0vivo studies. Model predictions captured observed concentrations of amiodarone in pediatric patients with ECMO well with an average fold error between 0.5 and 2. Model simulations support an amiodarone intravenous (i.v) bolus dose of 22\u2009mg\/kg (neonates), 13\u2009mg\/kg (infants), 8\u2009mg\/kg (children), and 6\u2009mg\/kg (adolescents). This PBPK modeling approach can be applied to explore the dosing of other drugs used in children on ECMO.<\/jats:p>","DOI":"10.1002\/psp4.13199","type":"journal-article","created":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T14:36:35Z","timestamp":1721572595000},"page":"1542-1553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A physiologically\u2010based pharmacokinetic modeling approach for dosing amiodarone in children on ECMO"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-9054","authenticated-orcid":false,"given":"Venkata K.","family":"Yellepeddi","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Department of Molecular Pharmaceutics College of Pharmacy, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Porter","family":"Hunt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-3797","authenticated-orcid":false,"given":"Danielle J.","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Division of Pediatric Critical Care, Department of Pediatrics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-2991","authenticated-orcid":false,"given":"Autumn","family":"McKnite","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-3183","authenticated-orcid":false,"given":"Aviva","family":"Whelan","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Division of Pediatric Critical Care, Department of Pediatrics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Watt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics, Spencer Fox Eccles School of Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Division of Pediatric Critical Care, Department of Pediatrics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Extracorporeal Membrane Oxygenation in Children","author":"Rosario DC","year":"2023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.21037\/acs.2018.09.08"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003622"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12338"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc11679"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2017.11.02"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-038505B"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600730632"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02004505"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1051\/ject\/202153068"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14050974"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2257"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-013-9451-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010395938"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1996.tb04177.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(00)01396-5"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004268446"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00562807"},{"key":"e_1_2_10_20_1","unstructured":"Pharmacokinetics Pharmacodynamics and Safety profile of understudied drugs administered to children per standard of care (POPS) (POPS or POP02). 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