{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:58:32Z","timestamp":1790017112433,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HHSN275201000003I"],"award-info":[{"award-number":["HHSN275201000003I"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K23HD083465"],"award-info":[{"award-number":["K23HD083465"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD096435"],"award-info":[{"award-number":["R01HD096435"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included <jats:italic>a priori<\/jats:italic> in the model. Using the final model, the steady\u2010state maximum concentrations (C<jats:sub>ss,max<\/jats:sub>) and the area under the metoclopramide plasma concentration\u2010time curve at steady state from 0 to 6 hours (AUC<jats:sub>ss,0\u20136h<\/jats:sub>) were simulated following 0.1 or 0.15 mg\/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two\u2010compartment model with first\u2010order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01\u201319.13]). There were 20 infants (\u2264 2 years), 9 children (2 years to age \u2264 12 years), and 21 adolescents (&gt; 12 years). Body weight was the only covariate included in the final model. For &gt; 75% of virtual patients, simulated C<jats:sub>ss,max<\/jats:sub> and AUC<jats:sub>ss,0\u20136h<\/jats:sub> estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients &lt; 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg\/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux.<\/jats:p>","DOI":"10.1111\/cts.12803","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T12:56:13Z","timestamp":1587646573000},"page":"1189-1198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents"],"prefix":"10.1111","volume":"13","author":[{"given":"Shufan","family":"Ge","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan R.","family":"Mendley","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline G.","family":"Gerhart","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Melloni","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Hornik","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina USA"},{"name":"Department of Pediatrics Duke University School of Medicine Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice E.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Kosair Charities Pediatric Clinical Research Unit Department of Pediatrics University of Louisville Louisville Kentucky USA"},{"name":"Norton Children's Hospital Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Atz","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Children's Hospital Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Delmore","sequence":"additional","affiliation":[{"name":"Wesley Medical Center Wichita Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Tremoulet","sequence":"additional","affiliation":[{"name":"School of Medicine University of California\u2010San Diego San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barrie","family":"Harper","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Payne","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Lin","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinson","family":"Erinjeri","sequence":"additional","affiliation":[{"name":"The Emmes Company, LLC Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cohen\u2010Wolkowiez","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina USA"},{"name":"Department of Pediatrics Duke University School of Medicine Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics UNC Eshelman School of Pharmacy The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Best Pharmaceuticals for Children Act \u2013 Pediatric Trials Network Steering Committee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1159\/000092876"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-2664"},{"key":"e_1_2_10_3_1","unstructured":"US Food and Drug Administration (FDA).FDA web site. 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