Physiologically‐based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co‐administered with ritonavir

Author:

Sun Zexu123,Zhao Nan1ORCID,Xie Ran1,Jia Bo1,Xu Junyu1,Luo Lin4,Zhuang Yulei4,Peng Yuyu4,Liu Xinchang4,Zhang Yingjun4,Zhao Xia1,Liu Zhaoqian256,Cui Yimin37

Affiliation:

1. Drug Clinical Trial Institution Peking University First Hospital Beijing China

2. Department of Pharmacology, Xiangya School of Pharmaceutical Sciences Central South University Changsha China

3. Institute of Clinical Pharmacology, Peking University Beijing China

4. Sunshine Lake Pharma Co., Ltd Dongguan China

5. Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University Changsha China

6. Institute of Clinical Pharmacology, Engineering Research Center for applied Technology of Pharmacogenomics of Ministry of Education Central South University Changsha China

7. Department of Pharmaceutical Administration and Clinical Pharmacy, School of Pharmaceutical Sciences Peking University Beijing China

Abstract

AbstractGLS4 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.

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3