Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China

Mengyang Yu; Shupeng Liu; Xiaofei Wu; Hongyun Wang

doi:10.3389/fphar.2023.1306222

Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China

Front Pharmacol. 2024 Jan 10:14:1306222. doi: 10.3389/fphar.2023.1306222. eCollection 2023.

Authors

Mengyang Yu¹, Shupeng Liu¹, Xiaofei Wu¹, Hongyun Wang¹

Affiliation

¹ Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Abstract

Aims: This study aimed to develop a population pharmacokinetic (PopPK) model of ilaprazole in healthy subjects and patients with duodenal ulcer in Chinese and investigate the effect of potential covariates on pharmacokinetic (PK) parameters. Methods: Pharmacokinetic data from 4 phase I clinical trials and 1 phase IIa clinical trial of ilaprazole were included in PopPK analysis. Phoenix NLME 8.3 was used to establish a PopPK model and quantify the effects of covariate, such as demographic data, biochemical indicators and disease state on the PK parameters of ilaprazole. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and visual predictive check. Results: A two-compartment model with first-order elimination successfully described the pharmacokinetic properties of ilaprazole. In the final PopPK model, body weight and sex were identified as statistically significant covariates for volume of peripheral compartment (V_p) and clearance of central compartment (CL), respectively, and disease status was also screened as a significant covariate affecting both CL and V_p. The validation results demonstrated the good predictability of the model, which was accurate and reliable. Conclusion: This is the first population pharmacokinetics study of ilaprazole in the Chinese, and the PopPK model developed in this study is expected to be helpful in providing relevant PK parameters and covariates information for further studies of ilaprazole.

Keywords: Chinese population; ilaprazole; modeling and simulation; population pharmacokinetics; proton pump inhibitors.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by National High Level Hospital Clinical Research Funding (2022-PUMCH-B-118).