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Development of a Korean‐specific virtual population for physiologically based pharmacokinetic modelling and simulation
Author(s) -
Kim Yun,
Hatley Oliver,
Rhee Sujin,
Yi Sojeong,
Lee Hyun A.,
Yoon Sumin,
Chung JaeYong,
Yu KyungSang,
Lee Howard
Publication year - 2019
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2178
Subject(s) - pharmacology , pharmacokinetics , population , physiologically based pharmacokinetic modelling , rosuvastatin , drug , nonmem , medicine , environmental health
Physiologically based pharmacokinetic (PBPK) modelling 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 drug metabolizing enzymes (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 PKs of a drug, particularly in various stages of drug development.