Model-based exploration of the rationality of off-label use of cetirizine in Chinese pediatric patients: a prospective cohort study

Wei Liu; Zhiyuan Tan; Ping Yang; Zhiheng Yu; Xueting Yao; Pengxiang Zhou; Ling Liu; Wei Zhou

doi:10.3389/fphar.2024.1322788

Model-based exploration of the rationality of off-label use of cetirizine in Chinese pediatric patients: a prospective cohort study

Front Pharmacol. 2024 Mar 14:15:1322788. doi: 10.3389/fphar.2024.1322788. eCollection 2024.

Authors

Wei Liu^#^{1

2

3}, Zhiyuan Tan^#¹, Ping Yang^#^{1

2}, Zhiheng Yu⁴, Xueting Yao⁵, Pengxiang Zhou^{1

3}, Ling Liu⁶, Wei Zhou⁶

Affiliations

¹ Department of Pharmacy, Peking University Third Hospital, Beijing, China.
² Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing, China.
³ Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China.
⁴ Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
⁵ Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
⁶ Department of Pediatrics, Peking University Third Hospital, Beijing, China.

^# Contributed equally.

Abstract

Aims: Cetirizine is frequently administered at an increased dosage in clinical practice and recommended by several guidelines. Nonetheless, the pharmacokinetic (PK) profile and real-world safety data remain insufficient in the Chinese pediatric population. The objective of the current study is to develop a population pharmacokinetic (PPK) model for cetirizine in Chinese pediatric patients and to investigate the rationale behind its off-label usage. Methods: A prospective cohort study was conducted, enrolling children who had been diagnosed with allergic diseases and prescribed cetirizine. The outcomes were safety and pharmacokinetic (PK) parameters. Cetirizine concentrations were measured using a pre-established analytical method. Subsequently, a PK model was developed, followed by model evaluation and simulation. The developed PK model was employed to investigate the drug exposure differences across various age groups and to simulate scenarios of potential overdose. Results: Sixty-three children were enrolled, and 24 of them received a cetirizine dose exceeding the recommended dosage. A PPK model, based on published literature, served as the basis of our analysis, with adjustment made to estimate certain parameters. The final model evaluation and validation indicated accurate predictive performance and robust parameter estimation. Simulations conducted for the label-dose among age 1-12 indicated median maximum concentration at steady state (C_max,ss) of 7 year old children could be the highest. The model was also used to predict the off-label dose scenarios and overdose patient to support the clinical decision. There were no adverse drug reactions in either group. Conclusion: This study provides evidence-based and model-based exploration for optimizing cetirizine usage in Chinese pediatric patients. The cetirizine PPK model showed accurate predictive performance and could be utilized to simulate individual patient exposure in real-world clinical scenarios.

Keywords: allergic diseases; antihistamines; cetirizine; modeling and simulation; off-label use; population pharmacokinetics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was carried out by the support of National Science and Technology Major Project (2017ZX09304029-005-02).