Open AccessPopulation Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents
Author(s) -
Ge Shufan,
Mendley Susan R.,
Gerhart Jacqueline G.,
Melloni Chiara,
Hornik Christoph P.,
Sullivan Janice E.,
Atz Andrew,
Delmore Paula,
Tremoulet Adriana,
Harper Barrie,
Payne Elizabeth,
Lin Susan,
Erinjeri Jinson,
CohenWolkowiez Michael,
Gonzalez Daniel
Publication year - 2020
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12803
Subject(s) - metoclopramide , medicine , enteral administration , nonmem , pharmacokinetics , dosing , reflux , population , antiemetic , pediatrics , anesthesia , parenteral nutrition , vomiting , disease , environmental health
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 a priori in the model. Using the final model, the steady‐state maximum concentrations (C ss,max ) and the area under the metoclopramide plasma concentration‐time curve at steady state from 0 to 6 hours (AUC ss,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 C ss,max and AUC ss,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.