PBPK Modeling of Coproporphyrin I Reveals Frailty-Associated Changes in Hepatic OATP1B1 Function in Chinese Adults
- Journal
- Clinical pharmacokinetics (Q1)
- Published
- 21 September 2026
- Study design
- Unclassified
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Longjie Li, Mengfan Ye, Wenhang Xu, Xinyan Zhu, Like Xie, Haiping Xu, et al.
- PMID
- 42766276
- DOI
- 10.1007/s40262-026-01704-7
Why clinicians should know about it
- Picked for Pharmacology (medical) (paper of the day, 24 September 2026): PBPK model of CPI, OATP1B1 function
Abstract
OBJECTIVES: Understanding 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. METHODS: Serum 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®. External PBPK models for Caucasian, Indian, and Japanese populations were constructed using reported CPI synthesis rates. Model-based simulations were performed to evaluate frailty-associated changes in OATP1B1 function and rosuvastatin exposure under different dosing scenarios. RESULTS: Coproporphyrin 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. CONCLUSIONS: This 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.
Abstract as published, via PubMed.
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