A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept

doi:10.1124/dmd.123.001344

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	A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept
	Sugiyama, Yuichi1,2,4 ; Aoki, Yasunori 1,3
	2023-09-01
发表期刊	DRUG METABOLISM AND DISPOSITION (IF:4.4[JCR-2023],3.7[5-Year])
ISSN	0090-9556
EISSN	1521-009X
卷号	51 期号:9
发表状态	已发表
DOI	10.1124/dmd.123.001344
摘要	Understanding the extended clearance concept and establishing a physiologically based pharmacokinetic (PBPK) model are crucial for investigating the impact of changes in transporter and metabolizing enzyme abundance/functions on drug pharmacokinetics in blood and tissues. This mini-review provides an overview of the extended clearance concept and a PBPK model that includes transporter-mediated uptake processes in the liver. In general, complete in vitro and in vivo extrapolation (IVIVE) poses challenges due to missing factors that bridge the gap between in vitro and in vivo systems. By considering key in vitro parameters, we can capture in vivo pharmacokinetics, a strategy known as the top-down or middle-out approach. We present the latest progress, theory, and practice of the Cluster Gauss-Newton method, which is used for middle-out analyses. As examples of poor IVIVE, we discuss "albumin-mediated hepatic uptake" and "time -dependent inhibition" of OATP1Bs. The hepatic uptake of highly plasma bound drugs is more efficient than what can be accounted for by their unbound concentration alone. This phenomenon is referred to as "albumin-mediated" hepatic uptake. IVIVE was improved by measuring hepatic uptake clearance in vitro in the presence of physiologic albu- min concentrations. Lastly, we demonstrate the application of Cluster Gauss-Newton method-based analysis to the target-mediated drug disposition of bosentan. Incorporating saturable target binding and OATP1B-mediated hepatic uptake into the PBPK model enables the consideration of nonlinear kinetics across a wide dose range and the prediction of receptor occupancy over time.
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Japan Society for the Promotion of Science["22H02789","22K19388"]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Pharmacology & Pharmacy
WOS记录号	WOS:001089195500002
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
引用统计	被引频次：11[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/346498
专题	iHuman研究所 iHuman研究所_特聘教授组_Yuichi Sugiyama组
通讯作者	Sugiyama, Yuichi
作者单位	1.Josai Int Univ, Lab Quantitat Syst Pharmacokinet Pharmacodynam, Chiyoda Ku, Tokyo, Japan 2.ShanghaiTech Univ, iHuman Inst, Shanghai, Peoples R China 3.AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab, Drug Metab & Pharmacokinet Res & Early Dev, Gothenburg, Sweden 4.Josai Int Univ, Lab Quantitat Syst Pharmacokinet Pharmacodynam, 2-3-11 Hirakawa Cho,Chiyoda Ku, Tokyo 1020093, Japan
第一作者单位	iHuman研究所
通讯作者单位	iHuman研究所
推荐引用方式 GB/T 7714	Sugiyama, Yuichi,Aoki, Yasunori. A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept[J]. DRUG METABOLISM AND DISPOSITION,2023,51(9).
APA	Sugiyama, Yuichi,&Aoki, Yasunori.(2023).A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept.DRUG METABOLISM AND DISPOSITION,51(9).
MLA	Sugiyama, Yuichi,et al."A 20-Year Research Overview: Quantitative Prediction of Hepatic Clearance Using the In Vitro-In Vivo Extrapolation Approach Based on Physiologically Based Pharmacokinetic Modeling and Extended Clearance Concept".DRUG METABOLISM AND DISPOSITION 51.9(2023).