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Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Quantitative Evaluation of Drug-Drug Interaction Potentials by in vivo Information- Guided Prediction Approach

Author(s): Feng Chen, Zhe-Yi Hu, Wei-Wei Jia, Jing-Tao Lu and Yuan-Sheng Zhao

Volume 15, Issue 8, 2014

Page: [761 - 766] Pages: 6

DOI: 10.2174/1389200216666150223151758

Price: $65


Drug-drug interaction (DDI) is one important topic in drug discovery, drug development and clinical practice. Recently, a novel approach, in vivo information-guided prediction (IVIP), was introduced for predicting the magnitude of pharmacokinetic DDIs which are caused by changes in cytochrome P450 (CYP) activity. This approach utilizes two parameters, i.e. CR (the apparent contribution of the target metabolizing enzyme to the clearance of the substrate drug) and IX (the apparent effect of a perpetrator on the target CYP) to describe the magnitude of DDI between a perpetrator and a victim drug. The essential concept of this method assumes that at a given dose level, the IX for a given perpetrator remains constant whatever the victim drug is. Usually, this IVIP method is only based on information from clinical studies and does not need in vitro information. In this review, basic concept, application and extension, as well as pros and cons of the IVIP method were presented. How to apply this approach was also discussed. Thus far, this method displayed good performance in predicting DDIs associated with CYPs, and can be used to forecast the magnitude of a large number of possible DDIs, of which only a small portion have been investigated in clinical studies. The key concept of this static approach could even be implemented in dynamic modeling to assess risks of DDIs involving drug transporters.

Keywords: Drug-drug interaction, in vivo information-guided, prediction method.

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