Physiologically‐Based Pharmacokinetic Modeling of Omalizumab to Predict the Pharmacokinetics and Pharmacodynamics in Pediatric Patients

Omalizumab is widely used in clinical practice; however, knowledge gaps in the dosage of omalizumab for children aged 2-6 years with moderate-to-severe persistent allergic asthma have been identified. The aim of this study was to explore dosing regimens for moderately-to-severely allergic pediatric patients aged 2-6 years. The physiologically-based pharmacokinetic (PBPK) model of omalizumab was developed and verified in adult patients, extrapolated to pediatric patients, and simulated for omalizumab by adding two observation chambers (free IgE and total IgE). The simulation results showed that the fold errors of the predicted and observed values of the area under the curve (AUC) and peak plasma concentration (C_max ) were between 0.5 and 2.0, and the average folding error and the absolute average folding error values for all concentration-time data points were 1.09 and 1.48, respectively. The PBPK model combined with pharmacokinetic/pharmacodynamic analysis of omalizumab demonstrated that both the model-derived dose and the original dose could control the average free IgE of 2-6-year-old children with moderate-to-severe allergic asthma below 25 ng/mL, and some of the model-derived doses were lower. This conclusion provides a basis for the selection of dosage in clinical practice reference.