ArticleBritish journal of clinical pharmacology2026
Application of paediatric cetirizine PBPK model to guide precision medicine and understand renal P-glycoprotein ontogeny.
Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Application of paediatric cetirizine PBPK model to guide precision medicine and understand renal P-glycoprotein ontogeny.British journal of clinical pharmacology · 2026Article
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8 authors.
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Abstract
aimCetirizine is widely used to treat children with allergic rhinitis and urticaria, yet optimal doses are undefined. Limited pharmacokinetic (PK) data and undefined renal P-glycoprotein (P-gp) ontogeny hinder the direct extrapolation of dosing from adults to children. This study aims to develop a paediatric cetirizine physiologically based pharmacokinetic (PBPK) model to explore renal P-gp ontogeny and guide optimal dosing strategies.
methodsAn adult PBPK model for cetirizine was developed to determine drug-specific parameters. Combining the age-dependent physiological parameters embedded in SimCYP® and cetirizine PK from Caucasian children of varying ages to infer renal P-gp ontogeny, the paediatric cetirizine PBPK model was constructed. The ontogeny was validated using PK data from Chinese children across various age groups. The validated model was then employed to evaluate optimal dosing regimens for children in different age groups.
resultsThe renal P-gp ontogeny equation was successfully inferred and incorporated into the PBPK model, capturing 100% and 87.8% of the observed PK data in Caucasian and Chinese children within the 90% prediction interval, respectively. Simulation results suggest that 5 mg twice daily (BID) for children aged 6-12 years and 0.25 mg/kg BID for children under 6 years are optimal, whereas fixed doses of 5 mg once-daily (QD) for children aged 2-6 years and 2.5 mg BID for children aged 0.5-2 years are also appropriate.
conclusionUtilizing PBPK modelling and simulation, this study elucidated P-gp ontogeny and recommended the optimal cetirizine dosage regimen for children across all age groups.
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