Evidence map›Paper›PMID 42766276›Full record

ArticleClinical pharmacokinetics2026

PBPK Modeling of Coproporphyrin I Reveals Frailty-Associated Changes in Hepatic OATP1B1 Function in Chinese Adults.

Longjie Li, Mengfan Ye, Wenhang Xu, Xinyan Zhu, Like Xie, Haiping Xu, Qingfeng He, Xiao Zhu, Xiaoqiang Xiang, Juan Xie

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Article in Clinical pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Longjie Li *Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0009-0003-4653-290X
Mengfan Ye *Department of General Medicine at Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Wenhang XuDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China.
Xinyan ZhuDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China.
Like XieCollege of Pharmacy, Shenzhen Technology University, Shenzhen, China.
Haiping XuDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China.
Qingfeng HeDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China.
Xiao ZhuDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China.
Xiaoqiang XiangDepartment of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai, China. xiangxq@fudan.edu.cn.ORCID http://orcid.org/0000-0002-8683-2603
Juan XieDepartment of General Medicine at Shanghai Fifth People's Hospital, Fudan University, Shanghai, China. abclux@126.com.

Funding

This scientific research was funded by Shanghai Fifth People 's Hospital, Fudan University No. 2023WYRH10
6 · The paper itself

Abstract

objectivesUnderstanding variability in hepatic organic anion transporting polypeptide 1B1 (OATP1B1) activity is essential for optimizing drug therapy and predicting drug-drug interactions. Coproporphyrin I (CPI) is an endogenous OATP1B1 substrate and a noninvasive biomarker of transporter function. However, CPI disposition in Chinese adults remains insufficiently characterized. This study aimed to characterize CPI variability in Chinese adults and apply physiologically based pharmacokinetic (PBPK) modeling to quantify OATP1B1 variability and explore clinical implications.

methodsSerum CPI concentrations were measured in 122 Chinese inpatients. Variability across age, sex, and frailty status was evaluated. Coproporphyrin I-specific disposition processes were implemented and parameterized within the standard whole-body PBPK structure of PK-Sim

resultsCoproporphyrin I concentrations increased with age and frailty severity. PBPK analyses suggested that hepatic OATP1B1 functional abundance in frail Chinese older adults may be reduced by approximately 40.9% relative to non-frail individuals. The PBPK model reproduced CPI disposition across demographic subgroups and external populations. Simulations indicated that rosuvastatin exposure increased from adults to non-frail elderly and further to frail elderly individuals, with exposure at 5 mg in frail elderly individuals comparable to that at 10 mg in adults.

conclusionsThis study provides a PBPK framework for interpreting CPI variability and quantifying frailty-associated changes in OATP1B1 function in Chinese adults, supporting biomarker-informed precision dosing of OATP1B1 substrate drugs.

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PMID42766276

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