(T-111) Population Pharmacokinetics of Levocetirizine in Children with Uncontrolled Allergic Asthma: An Ongoing Study

Syed Saoud Zaidi, PharmD , PhD – Indiana Univeristy; Bridgette Jones, MS, MD – University of Missouri-Kansas City School of Medicine; Michael Heathman, MS – Indiana Univeristy; Brian Overholser, PharmD – Purdue University; Lais Da Silva – Indiana Univeristy; Sara Quinney, PharmD , PhD – Indiana Univeristy

Objectives: This study is part of an ongoing effort to improve precision therapy in pediatric asthma by integrating pharmacokinetics (PK) with biomarker-based pharmacodynamics. Levocetirizine (LTZ), a selective H1-antihistamine, is being evaluated for its ability to improve asthma control when added to guideline-based therapy in children with uncontrolled persistent allergic asthma. The study employs Histamine Iontophoresis with Laser Doppler (HILD) as a novel, non-invasive pharmacodynamic biomarker to classify participants into hyper- and hypo-responsive phenotypes based on their histamine response.
The objective of this study is to develop a population pharmacokinetic (PopPK) model of LTZ in this population and quantify inter-individual variability in exposure. This model will support exposure–response analyses to determine whether HILD phenotype predicts clinical benefit from LTZ, enabling more targeted use of antihistamines in pediatric asthma.

Methods: As part of a randomized, double-blind, placebo-controlled 2×2 crossover trial, children aged 7–17 years received 5 mg (if < 40kg) or 10 mg (>40kg) oral doses of LTZ. At steady state, intensive PK sampling was performed up to 24 hours. PopPK modeling was conducted in Monolix (2024R1) using data from the first 18 participants. Covariate effects of log-transformed body weight were incorporated on clearance (CL) and central volume of distribution (V1) using fixed allometric functions (0.75 and 1.0, respectively). Other covariates were graphically evaluated, but not included in the model due to limited sample size.

Results: A two-compartment model with transit compartment absoprtion best described the data. Final model estimates were: Ktr = 21.5 h⁻¹, Mtt = 0.179 h, CL = 2.15 L/h, V1 = 9.79 L (RSE 14.6%), ka = 2.92 h⁻¹, Q = 8.31 L/h, V2 = 11.8 L. Interindividual variability (IIV) was moderate for CL (ω² = 0.391) and V1 (ω² = 0.568). Weight significantly explained variability in both CL and V1. Combined additive and proportional error model provided adequate fit. The model adequately captured observed concentrations, and parameter precision was acceptable. Evaluation of exposure–response relationships with asthma control outcomes is ongoing.

Conclusions: This PopPK model describes LTZ disposition in children with asthma and supports future simulations and covariate-based dosing refinement. Integration with ongoing clinical data will enable exposure–response analyses and inform precision dosing strategies. The study is currently ongoing.

Citations: 1. Liu, X., Jones, B.L., Roberts, J.K. et al. Population pharmacokinetic/pharmacodynamic modeling of histamine response measured by histamine iontophoresis laser Doppler. J Pharmacokinet Pharmacodyn 43, 385–393 (2016). https://doi.org/10.1007/s10928-016-9478-9
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Keywords: Asthma, Pediatric Allergy, Levocetirizine