Strategies of clinical drug-drug interaction studies and application progress of physiologically-based pharmacokinetic model

doi:10.12092/j.issn.1009-2501.2019.10.002

Abstract

Abstract:

Drug-drug interaction (DDI) might cause reduced efficacy, even induce severe safety issues of drugs, which might be one of the most common concerns in clinical therapy. Therefore, clinical DDI should be investigated during new drug development before marketing. This paper reviewed the overall research strategy and types of DDI studies. Regarding various mathematical models, physiologically-based pharmacokinetics model (PBPK) had become an important tool to assist or even partially replace DDI studies by integrating human physiological parameters, drug chemical/physical data, and drug mechanistic pharmacokinetic data to predict pharmacokinetic characteristics. Recently, PBPK analyses had been extensively applied in DDI studies in America and Europe, where relevant guidance documents had been released to direct such studies，whereas Chinese guidance on PBPK was absent. By seeing the power of model informed drug development to improve new drug research efficiency, in this review, we introduced the application of PBPK model in study design, waiver of DDI studies, and so on. How to evaluate the prediction accuracy and report PBPK study results was briefly summarized as well. Hopefully this paper could update knowledge and support new drug development in China.

Key words: drug-drug interaction, physiologically-based pharmacokinetic model, clinical developme

CLC Number:

R969.1

LI Li, YANG Jinbo. Strategies of clinical drug-drug interaction studies and application progress of physiologically-based pharmacokinetic model[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(10): 1085-1091.

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