Exploring the Influence of Obesity and CYP2 C19 Genotype on Lansoprazole Pharmacokinetics in Pediatric Patients: A Population Modeling Approach.

Document Type

Article

Publication Date

7-2025

Identifier

DOI: 10.1007/s40262-025-01517-0; PMCID: PMC12187529

Abstract

BACKGROUND AND OBJECTIVE: Pediatric pharmacokinetics pose unique challenges, particularly concerning drug dosing in the presence of obesity and genetic variability in drug-metabolizing enzymes such as cytochrome P450 (CYP) 2C19. This study aimed to develop a lansoprazole pediatric population pharmacokinetic (popPK) model considering obesity, obesity-associated changes in inflammatory cytokines and the liver, and CYP2C19 genotype, and to assess implications for dosing strategies.

METHODS: Pediatric subjects with and without obesity (6-21 years, n = 47) received one oral dose of 1.2 mg/kg fat-free mass (FFM), not exceeding 60 mg. Plasma concentrations were measured at multiple time points, and a popPK analysis using NONMEM with stepwise covariate modeling was performed. Simulations compared exposures between children without and with obesity (BMI percentile ≥ 95th) after two dosing strategies: U.S. Food and Drug Administration (FDA)-approved total body weight-tiered and FFM-based dosing.

RESULTS: A total of 537 lansoprazole concentrations were modeled using a two-compartment model with Weibull absorption and linear elimination. Parameters were allometrically scaled to FFM with fixed exponents of 0.75 for clearances and 1 for volumes. CYP2C19 was identified as a significant covariate for CL/F. No significant differences in lansoprazole exposure were observed between children with and without obesity, with both dosing approaches. Higher exposure was noted in poor/intermediate metabolizers of CYP2C19. FFM-based dosing led to similar levels of exposure between children (aged 6-11 years) and adolescents (aged 12-17 years).

CONCLUSIONS: Obesity was not associated with differences in lansoprazole pharmacokinetics in children. A FFM-based dosing approach could result in comparable exposure between children and adolescents. Dose adjustments are supported for poor/intermediate metabolizers of CYP2C19.

Journal Title

Clinical pharmacokinetics

Volume

64

Issue

7

First Page

1047

Last Page

1059

MeSH Keywords

Humans; Lansoprazole; Child; Adolescent; Female; Male; Genotype; Models, Biological; Cytochrome P-450 CYP2C19; Young Adult; Obesity; Proton Pump Inhibitors; Pediatric Obesity; Cytochrome P450 Family 2

PubMed ID

40379961

Keywords

Lansoprazole; Genotype; Biological Models; Cytochrome P-450 CYP2C19; Obesity; Proton Pump Inhibitors; Pediatric Obesity; Cytochrome P450 Family 2

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