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Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity
Author(s) -
Shakhnovich V.,
AbdelRahman S.,
Friesen C. A.,
Weigel J.,
Pearce R. E.,
Gaedigk A.,
Leeder J. S.,
Kearns G. L.
Publication year - 2019
Publication title -
pediatric obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.226
H-Index - 69
eISSN - 2047-6310
pISSN - 2047-6302
DOI - 10.1111/ijpo.12459
Subject(s) - pantoprazole , dosing , medicine , pharmacokinetics , obesity , proton pump inhibitor , pharmacodynamics , gastroenterology , pharmacology , omeprazole
Summary 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.