Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.
CPT Pharmacometrics Syst Pharmacol
; 2024 Jun 20.
Article
in En
| MEDLINE
| ID: mdl-39031849
ABSTRACT
GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that is co-administered with ritonavir to maintain the anticipated concentration required for the effective antiviral activity of GLS4. In this study, the first physiologically-based pharmacokinetic (PBPK) model for GLS4/ritonavir was successfully developed. The predictive performance of the PBPK model was verified using data from 39 clinical studies, including single-dose, multiple-dose, food effects, and drug-drug interactions (DDI). The PBPK model accurately described the PK profiles of GLS4 and ritonavir, with predicted values closely aligning with observed data. Based on the verified GLS4/ritonavir model, it prospectively predicts the effect of hepatic impairment (HI) and DDI on its pharmacokinetics (PK). Notably, CYP3A4 inducers significantly influenced GLS4 exposure when co-administered with ritonavir; co-administered GLS4 and ritonavir significantly influenced the exposure of CYP3A4 substrates. Additionally, with the severity of HI increased, there was a corresponding increase in the exposure to GLS4 when co-administered with ritonavir. The GLS4/ritonavir PBPK model can potentially be used as an alternative to clinical studies or guide the design of clinical trial protocols.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
CPT Pharmacometrics Syst Pharmacol
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States