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Using physiologically based pharmacokinetic modelling to optimize repaglinide and irbesartan dosing in Chinese
Yujie Wen1, Zexu Sun2, Hongyi Tan3
1Department of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
British Journal of Clinical Pharmacology
|August 13, 2026
Summary
Physiologically based pharmacokinetic (PBPK) models were developed for irbesartan (IRB) and repaglinide (REP). The PBPK model predicted increased REP exposure in SLCO1B1 c.521TT genotype individuals, guiding individualized dosing recommendations.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pharmacogenomics
- Computational Biology
Background:
- Drug-drug interactions (DDIs) pose significant clinical challenges, particularly in individuals with specific genetic polymorphisms.
- The SLCO1B1 c.521T>C gene polymorphism influences the pharmacokinetics of various drugs, including repaglinide (REP).
- Irbesartan (IRB) is often co-prescribed, necessitating an understanding of its interaction with REP in genetically diverse populations.
Purpose of the Study:
- To develop physiologically based pharmacokinetic (PBPK) models for irbesartan (IRB) and repaglinide (REP).
- To apply the developed REP/IRB PBPK model to characterize the DDI between REP and IRB in individuals with the SLCO1B1 c.521T>C gene polymorphism.
- To predict REP exposure and provide dose adjustment recommendations for the SLCO1B1 c.521TT genotype population.
Main Methods:
- Literature review and laboratory data were utilized to construct the PBPK models.
- Key parameters within the PBPK models were optimized for accuracy.
- Published clinical study data were employed to validate the predictive performance of the PBPK models.
Main Results:
- The REP/IRB PBPK model accurately described plasma concentration-time profiles, AUC, Cmax, and Tmax.
- Co-administration of IRB significantly increased REP exposure in individuals with the SLCO1B1 c.521TT genotype compared to those with the c.521TC genotype.
- For SLCO1B1 c.521TT individuals, REP administration 2 hours earlier or 4 hours later, or at 60-70% of the initial dose, was recommended when co-administered with 300mg IRB.
Conclusions:
- A robust PBPK model for REP and IRB was successfully developed.
- The PBPK model effectively predicted DDIs in the context of the SLCO1B1 c.521T>C gene polymorphism.
- Individualized drug dosing recommendations were provided for the SLCO1B1 c.521TT genotype population, enhancing therapeutic safety and efficacy.
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