Population Pharmacokinetics of Ropeginterferon Alfa-2b: A Comparison Between Healthy Caucasian and Chinese Subjects

Min Zhu; Mei-Xia Wang; Zi-Ran Li; Wei Wang; Xia Su; Zheng Jiao

doi:10.3389/fphar.2021.673492

Population Pharmacokinetics of Ropeginterferon Alfa-2b: A Comparison Between Healthy Caucasian and Chinese Subjects

Front Pharmacol. 2021 May 28:12:673492. doi: 10.3389/fphar.2021.673492. eCollection 2021.

Authors

Min Zhu^{1

2}, Mei-Xia Wang³, Zi-Ran Li^{1

4}, Wei Wang⁵, Xia Su⁶, Zheng Jiao¹

Affiliations

¹ Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
² School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
³ National Clinical Trial Institution Office and Phase I Study Ward, Beijing Youan Hospital, Capital Medical University, Beijing, China.
⁴ Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
⁵ PharmaEssentia Biotechnology (Beijing) Limited, Beijing, China.
⁶ Pharmacometrics, Earnest and Ye-sayer, Beijing, China.

Abstract

Objective: To develop a population pharmacokinetic (PK) model for ropeginterferon alfa-2b and to compare its PK properties between Caucasian and Chinese populations. Methods: A population PK model was developed based on data from two phase I clinical trials conducted in Caucasian and Chinese individuals, to evaluate the influence of ethnicity on the PKs of ropeginterferon alfa-2b. Results: We included 456 observations from 30 healthy Caucasian subjects and 438 observations from 27 healthy Chinese subjects in the population PK analysis. The PKs of ropeginterferon alfa-2b were best described by a one-compartment quasi-equilibrium approximated target-mediated drug disposition model with first-order absorption and absorption lag times. The typical value (relative standard error%) of apparent clearance (CL/F) and volume of distribution of ropeginterferon alfa-2b in 70-kg subjects were 0.778 (12%) L/day and 2.32 (14%) L, respectively. Body weight was the only significant factor affecting the CL/F. There were no obvious differences in the PK properties of ropeginterferon alfa-2b, and predicted steady-state exposure was similar in the Chinese and Caucasian populations. Conclusion: No significant ethnic differences in ropeginterferon alfa-2b PKs were observed between the Chinese and Caucasian populations.

Keywords: Caucasian; Chinese; ethnic difference; nonlinear mixed effect modeling; population pharmacokinetics; ropeginterferon alfa-2b; target-mediated drug disposition.