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Development of a Korean-specific virtual population for physiologically-based pharmacokinetic modeling and simulation.

Biopharm Drug Dispos. 2019 Mar 28;:

Authors: Kim Y, Hatley O, Rhee SJ, Yi S, Lee HA, Yoon S, Chung JY, Yu KS, Lee H

Physiologically based pharmacokinetic (PBPK) modeling and simulation is a useful tool in predicting the PK profiles of a drug, assessing the effects of covariates such as demographics, ethnicity, genetic polymorphisms, and disease status on the PK, and evaluating the potential of drug-drug interactions. We developed a Korean-specific virtual population for the SimCYP® Simulator (version 15 used) and evaluated the population’s predictive performance using six substrate drugs (midazolam, S-warfarin, metoprolol, omeprazole, lorazepam, and rosuvastatin) of five major DMEs and two transporters. Forty-three parameters including the proportion of phenotypes in DMEs and transporters were incorporated into the Korean-specific virtual population. The simulated concentration-time profiles in Koreans were overlapped with most of the observed concentrations for the selected substrate drugs with a <2-fold difference in clearance. Furthermore, we found some drug models within the SimCYP® library can be improved, e.g., the minor allele frequency of ABCG2 and the fraction metabolized by UGT2B15 should be incorporated for rosuvastatin and lorazepam, respectively. The Korean-specific population can be used to evaluate the impact of ethnicity on the pharmacokinetics of a drug, particularly in various stages of drug development.

PMID: 30921829 [PubMed – as supplied by publisher]

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