Ropeginterferon alfa-2b contains a PEGylated isomer at only one position ( Illes et al., 2020), whereas PEG-Intron ® and Pegasys ® have 13 and six positional isomers, respectively ( Foster, 2004). Ropeginterferon alfa-2b (BESREMi ®) is a third-generation long-acting IFN injection marketed in the European Union for the treatment of polycythemia vera ( Gisslinger et al., 2015). Both drugs are administered weekly via subcutaneous (SC) injection. The first-generation long-acting IFN PEG-Intron ® ( Schering Corporation, 2001) from Merck and the second-generation Pegasys ® ( Genentech Inc., 2002) from Roche have been approved by the United States Food and Drug Administration and European Medicines Agency (EMA), to treat chronic hepatitis B and hepatitis C. Polyethylene glycol-modified (PEGylated) forms of IFN have considerably long half-lives and provide a means of improving patient compliance ( Pedder, 2003). Standard IFNs have short serum half-lives (approximately 6 h) ( Wills, 1990), which limits their use. There are three principal routes of IFN elimination: through the liver, the kidneys, or via interactions with IFN receptors ( Bocci, 1987). 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). 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. 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.Ĭonclusion: No significant ethnic differences in ropeginterferon alfa-2b PKs were observed between the Chinese and Caucasian populations. Body weight was the only significant factor affecting the CL/F. 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. 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.
Results: We included 456 observations from 30 healthy Caucasian subjects and 438 observations from 27 healthy Chinese subjects in the population PK analysis. 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. Objective: To develop a population pharmacokinetic (PK) model for ropeginterferon alfa-2b and to compare its PK properties between Caucasian and Chinese populations.