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dc.contributor.authorGe, S.
dc.contributor.authorMendley, S.R.
dc.contributor.authorBest Pharmaceuticals for Children Act - Pediatric Trials Network Steering Committee
dc.date.accessioned2020-06-08T20:21:03Z
dc.date.available2020-06-08T20:21:03Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85085489737&doi=10.1111%2fcts.12803&partnerID=40&md5=8d349df28452ef1cd2b6f677068887f0
dc.identifier.urihttp://hdl.handle.net/10713/13003
dc.description.abstractMetoclopramide 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 a priori in the model. Using the final model, the steady-state maximum concentrations (Css,max) and the area under the metoclopramide plasma concentration-time curve at steady state from 0 to 6 hours (AUCss,0-6h) 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-compartment model with first-order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01-19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (> 12 years). Body weight was the only covariate included in the final model. For > 75% of virtual patients, simulated Css,max and AUCss,0-6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients < 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. Copyright 2020 The Authors.en_US
dc.description.sponsorshiphis Pediatric Trials Network study was funded under National Institute of Child Health and Human Development (NICHD) con-tract HHSN275201000003I. D.G. receives salary support for research from the NICHD (K23HD083465 and R01HD096435). The content is solely the responsibility of the authors and does not necessarily repre-sent the official views of the National Institutes of Healthen_US
dc.description.urihttp://doi.org/10.1111/cts.12803en_US
dc.language.isoen_USen_US
dc.publisherBlackwell Publishing Ltden_US
dc.relation.ispartofClinical and Translational Science
dc.subjectpopulation pharmacokineticsen_US
dc.subject.lcshChildrenen_US
dc.subject.lcshYouthen_US
dc.subject.meshMetoclopramide--pharmacokineticsen_US
dc.titlePopulation Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescentsen_US
dc.typeArticleen_US
dc.identifier.doi10.1111/cts.12803
dc.identifier.pmid32324313


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