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KMID : 0811720210250060545
Korean Journal of Physiology & Pharmacology
2021 Volume.25 No. 6 p.545 ~ p.553
An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug
Hong Yun-Jung

Jeon Sang-Il
Choi Sue-In
Han Sung-Pil
Park Maria
Han Seung-Hoon
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 modelbased 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.
KEYWORD
Drug interactions, Half-Life, Model-based evaluation, Pharmacokinetics
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