Population Pharmacokinetic Model of Pegbing in Healthy Subjects and Chronic Hepatitis B Patients.

Abstract

Pegbing (peginterferon alpha-2b) is a polyethylene glycol-modified interferon α-2b injection that has demonstrated favorable efficacy and safety profiles in the treatment of chronic hepatitis B (CHB). This study aimed to develop a population pharmacokinetic (PopPK) model of Pegbing in both healthy subjects and CHB patients and to investigate the influence of covariates on its pharmacokinetic behavior. Pharmacokinetic data were obtained from a Phase I trial in healthy volunteers and a Phase II trial in CHB patients. A one-compartment model with a target-mediated drug disposition (TMDD) component incorporating IFN receptor downregulation was established to describe the pooled data from 28 healthy subjects and 39 CHB patients. Physiologically reasonable parameters were estimated, providing a good description and prediction of the model. Furthermore, the final PopPK model was externally validated using an independent dataset of 115 CHB patients. In the covariate analysis, health status (healthy v.s. CHB) was a significant covariate, affecting the Pegbing absorption rate, creatinine clearance was associated with clearance, and body weight affected the volume of distribution. Compared with healthy subjects, CHB patients exhibited a consistent area under the curve (AUC) but a higher C_max. A PopPK model of Pegbing in both healthy volunteers and CHB patients was successfully established. Based on the model simulation, covariate-based dose adjustment is unnecessary for CHB patients with normal renal function.