The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug

  • Hong, Yunjung (PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea) ;
  • Jeon, Sangil (Q-fitter, Inc.) ;
  • Choi, Suein (PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea) ;
  • Han, Sungpil (PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea) ;
  • Park, Maria (PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea) ;
  • Han, Seunghoon (PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, The Catholic University of Korea)
  • Received : 2021.04.23
  • Accepted : 2021.09.07
  • Published : 2021.11.01
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Abstract

Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and model-based analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.

Keywords

Acknowledgement

The authors wish to acknowledge the financial support of the Catholic Medical Center Research Foundation made in the program year of 2016.

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