Lee Se-in, undergraduate student at Sunchon National University College of Pharmacy, and research team led by Professor Jeong Seung-hyeon
A research paper co-authored by Lee Se-in, a sixth-year undergraduate student at Sunchon National University's College of Pharmacy, has been accepted for publication in Environmental Toxicology and Pharmacology, a prominent international SCIE journal in drug toxicology and pharmacokinetics.
The study was led by a research team under Professor Jeong Seung-hyeon of the university's pharmacy department. Lee served as first author and Jeong as corresponding author.
The research is also notable for having been carried out in connection with an undergraduate research practicum course.
The team built a physiologically based pharmacokinetic (PBPK) model for caffeine, the world's most widely consumed central nervous system stimulant.
Using the model, the team quantitatively predicted how caffeine exposure changes with declining liver function — not only in healthy individuals but also in patients with liver cirrhosis at Child-Pugh A and B stages.
Caffeine is metabolized in the body primarily by the CYP1A2 enzyme in the liver.
In patients with liver cirrhosis, reduced liver function diminishes metabolic capacity, meaning the same amount of caffeine can result in significantly higher systemic exposure than in healthy individuals.
Until now, research capable of quantitatively predicting such changes or proposing patient-tailored intake levels had been scarce.
The team constructed the PBPK model using domestic and international clinical pharmacokinetic data and verified its predictive accuracy across a range of doses.
The researchers then incorporated the pathophysiological changes seen in liver cirrhosis patients into the model, successfully reproducing the increase in caffeine exposure corresponding to varying degrees of liver function impairment.
The team also ran simulations of repeated caffeine intake and proposed an exposure-guided dosage adjustment strategy to keep systemic exposure in cirrhosis patients at levels equivalent to those in healthy individuals.
The findings suggest that, to maintain the same level of systemic exposure as healthy individuals, Child-Pugh A patients may need to reduce caffeine intake to approximately 51 percent of the normal amount, while Child-Pugh B patients may need to reduce it to around 18 percent.
Sensitivity analysis further confirmed that CYP1A2 metabolic activity, liver volume and changes in plasma protein binding are key factors determining caffeine exposure.
The results provide a foundation applicable not only to managing caffeine intake in liver disease patients but also to future research on optimizing drug dosing in patients with impaired liver function.
The study is considered one of the first to use a mechanism-based model built on real clinical data to quantitatively predict caffeine exposure in liver disease patients and propose an exposure-guided intake adjustment strategy.
"This study is significant in that it used a physiologically based pharmacokinetic model to quantitatively predict these changes and propose a patient-tailored caffeine intake strategy," Professor Jeong said.
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