Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

OBJECTIVE: To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials. STUDY DESIGN: A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula. Ten post-dose pantoprazole plasma concentrations were measured, and PK variables generated via noncompartmental methods (WinNonlin). Linear and nonlinear regression analyses and analyses of variance were used to explore obesity, age, and CYP2C19 genotype contribution to pantoprazole PK. PK variables of interest were compared with historic nonobese peers treated with pantoprazole. RESULTS: Independent of genotype, when normalized to dose per kg total body weight, pantoprazole apparent clearance and apparent volume of distribution were significantly lower (P < .05) and systemic exposure significantly higher (P < .01) in obese vs nonobese children. When normalized per kg LBW, these differences were not evident in children ≥12 years of age and markedly reduced in children <12 years of age. CONCLUSIONS: LBW dosing of pantoprazole led to pantoprazole PK similar to nonobese peers. Additional factors, other than body size (eg, age-related changes in CYP2C19 activity), appear to affect pantoprazole PK in children <12 years of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186652.

Full Text

Duke Authors

Cited Authors

  • Shakhnovich, V; Smith, PB; Guptill, JT; James, LP; Collier, DN; Wu, H; Livingston, CE; Zhao, J; Kearns, GL; Best Pharmaceuticals for Children Act – Pediatric Trials Network,

Published Date

  • February 2018

Published In

Volume / Issue

  • 193 /

Start / End Page

  • 102 - 108.e1

PubMed ID

  • 29389444

Pubmed Central ID

  • PMC5806153

Electronic International Standard Serial Number (EISSN)

  • 1097-6833

Digital Object Identifier (DOI)

  • 10.1016/j.jpeds.2017.10.011


  • eng

Conference Location

  • United States