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

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

doi:10.3389/fphar.2021.673492

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.

Highlights

Interferon (IFN) is produced in influenza virus-infected chick embryo cells, which has the ability to interfere with viral replication and induce resistance to viral infection
A total of 456 observations were from 30 Caucasian subjects, and 438 observations were from 27 Chinese subjects
We developed the first population PK model of repeginterferon alfa-2b using pooled data to investigate the nonlinear PKs and quantify the potential ethnic difference between Caucasians and Chinese populations

Summary

Introduction

Interferon (IFN) is produced in influenza virus-infected chick embryo cells, which has the ability to interfere with viral replication and induce resistance to viral infection. It has been widely used in the treatment of chronic hepatitis B (Janssen et al, 2005), hepatitis C (Rivero-Juarez et al, 2014), acquired immunodeficiency syndrome (Husak et al, 1997), and cancer (Bottomley et al, 2009). Standard IFNs have short serum half-lives (approximately 6 h). Polyethylene glycolmodified (PEGylated) forms of IFN have considerably long half-lives and provide a means of improving patient compliance (Pedder, 2003).

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Results

Discussion

Conclusion