Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity

Creator(s)

Valentina Shakhnovich, Children's Mercy HospitalFollow
Susan M. Abdel-Rahman, Children's Mercy HospitalFollow
Craig A. Friesen, Children's Mercy HospitalFollow
J. Weigel, UMKC School of Medicine
Robin E. Pearce, Children's Mercy HospitalFollow
Andrea Gaedigk, Children's Mercy HospitalFollow
J Steven Leeder, Children's Mercy HospitalFollow
G. L. Kearns, Arkansas Children's Hospital

Document Type

Article

Publication Date

1-2019

Identifier

10.1111/ijpo.12459; PMCID: PMC6309791

Abstract

© 2018 World Obesity Federation Background: Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing. Objective: To prospectively evaluate lean-body-weight-based (LBW) dosing of the PPI pantoprazole for children with and without obesity. Methods: Methods: Sixty-two children (6–17 years) received a one-time oral dose of liquid pantoprazole (1.2 mg kg −1 LBW). Plasma pantoprazole concentrations were measured at 10 time points over 8 h and pharmacokinetic (PK) profiles generated using non-compartmental techniques, in order to compare PK parameters of interest between children with and without obesity, while accounting for CYP2C19 genotype. Results: Adjusted for milligram-per-kilogram total body weight (TBW) pantoprazole received, apparent drug clearance (CL/F) was reduced 50% in children with vs. without obesity (p=0.03). LBW-based dosing compensated for this reduction in CL/F (p = 0.15). Conclusion: To achieve comparable systemic PPI exposures for children with and without obesity, we recommend using LBW, rather than TBW-based dosing for pantoprazole.

Journal Title

Pediatric Obesity

Volume

14

Issue

1

Keywords

CYP2C19; drug metabolism; pantoprazole; pediatric obesity

Comments

Grant support

• NICHD-2012-PAN01/Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatric Trials Network/International
• 1T32HD069038-05/National Institute of Child Health and Human Development/International
• T32 HD069038/HD/NICHD NIH HHS/United States
• 5T32HD069038-04/Childrens Mercy Hospital Fellowship Program in Pediatric Pharmacology/International
• The Children's Mercy Hospital/International

• L40 TR000598/TR/NCATS NIH HHS/United States

Recommended Citation

Shakhnovich V, Abdel-Rahman S, Friesen CA, et al. Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity. Pediatr Obes. 2019;14(1):10.1111/ijpo.12459. doi:10.1111/ijpo.12459