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

Area of Science:

• Pharmacology
• Pediatric Gastroenterology
• Obesity Medicine

Background:

• Children with obesity frequently experience gastroesophageal reflux disease (GERD).
• GERD treatment often involves proton pump inhibitors (PPIs), but pediatric dosing guidelines are lacking, particularly for obese children.
• This necessitates research into optimal dosing strategies for PPIs in pediatric populations.

Purpose of the Study:

• To prospectively assess the efficacy of lean-body-weight (LBW)-based dosing for pantoprazole in children.
• To compare the pharmacokinetic profiles of pantoprazole in children with and without obesity.
• To establish evidence-based dosing recommendations for pantoprazole in pediatric patients.

Main Methods:

• A prospective study involving 62 children aged 6-17 years.
• Administration of a single oral dose of pantoprazole (1.2 mg/kg LBW).
• Measurement of plasma pantoprazole concentrations over 8 hours to generate pharmacokinetic profiles, with adjustments for CYP2C19 genotype.

Main Results:

• Apparent drug clearance (CL/F) was 50% lower in children with obesity compared to those without, when adjusted for total body weight (TBW) dosing (p=0.03).
• Lean-body-weight (LBW)-based dosing effectively compensated for the reduced drug clearance in obese children (p=0.15).
• This suggests LBW dosing achieves comparable systemic exposure between the two groups.

Conclusions:

• Lean-body-weight (LBW)-based dosing of pantoprazole is recommended for children.
• This dosing strategy ensures comparable systemic proton pump inhibitor exposure in pediatric patients, irrespective of obesity status.
• LBW dosing provides a more accurate and equitable approach compared to total body weight (TBW) dosing for pantoprazole in children.