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Updated: Jul 12, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Physiologically based pharmacokinetic modeling of caffeine in patients with liver cirrhosis: Implications for
Se-In Lee1, Chi-Ho Lee1, Ji-Hun Jang2
1College of Pharmacy, Sunchon National University, 255 Jungang-ro, Suncheon-si, Jeollanam-do 57922, Republic of Korea.
Abstract:
Caffeine exposure may increase substantially in patients with liver cirrhosis due to impaired hepatic metabolism, but quantitative approaches for predicting exposure changes and guiding dose adjustment remain poorly defined. A physiologically-based-pharmacokinetic (PBPK) model of caffeine was developed using literature-derived clinical PK data from healthy adults and subsequently extrapolated to Child-Pugh A (CP-A) and Child-Pugh B (CP-B) cirrhotic populations by incorporating disease-specific physiological and biochemical changes. Most predicted PK parameters satisfied predefined two-fold error criterion. Repeated-dose simulations demonstrated progressive increases in systemic caffeine exposure with worsening hepatic impairment. Exposure-based simulations predicted that approximately 51% and 18% of healthy-subject dose would achieve comparable systemic exposure in CP-A and CP-B patients, respectively. Sensitivity analysis identified CYP1A2-related parameters, liver volume, plasma protein scale factor, and fraction unbound as major determinants of caffeine exposure. The developed PBPK model successfully characterized caffeine PKs and supports a simulation-based framework for predicting caffeine exposure under hepatic impairment.
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