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Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.
Sun, Zexu; Zhao, Nan; Xie, Ran; Jia, Bo; Xu, Junyu; Luo, Lin; Zhuang, Yulei; Peng, Yuyu; Liu, Xinchang; Zhang, Yingjun; Zhao, Xia; Liu, Zhaoqian; Cui, Yimin.
Afiliación
  • Sun Z; Drug Clinical Trial Institution, Peking University First Hospital, Beijing, China.
  • Zhao N; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
  • Xie R; Institute of Clinical Pharmacology, Peking University, Beijing, China.
  • Jia B; Drug Clinical Trial Institution, Peking University First Hospital, Beijing, China.
  • Xu J; Drug Clinical Trial Institution, Peking University First Hospital, Beijing, China.
  • Luo L; Drug Clinical Trial Institution, Peking University First Hospital, Beijing, China.
  • Zhuang Y; Drug Clinical Trial Institution, Peking University First Hospital, Beijing, China.
  • Peng Y; Sunshine Lake Pharma Co., Ltd, Dongguan, China.
  • Liu X; Sunshine Lake Pharma Co., Ltd, Dongguan, China.
  • Zhang Y; Sunshine Lake Pharma Co., Ltd, Dongguan, China.
  • Zhao X; Sunshine Lake Pharma Co., Ltd, Dongguan, China.
  • Liu Z; Sunshine Lake Pharma Co., Ltd, Dongguan, China.
  • Cui Y; Drug Clinical Trial Institution, Peking University First Hospital, Beijing, China.
CPT Pharmacometrics Syst Pharmacol ; 2024 Jun 20.
Article en 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: CPT Pharmacometrics Syst Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: CPT Pharmacometrics Syst Pharmacol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos