Quantitative evaluation of drug-drug interaction potentials by in vivo information-guided prediction approach

Feng Chen, Zhe Yi Hu, Wei Wei Jia, Jing Tao Lu, Yuan Sheng Zhao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)761-766
Number of pages6
JournalCurrent Drug Metabolism
Volume15
Issue number8
DOIs
StatePublished - Jan 1 2014

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Drug interactions
Drug Interactions
Pharmaceutical Preparations
Cytochrome P-450 Enzyme System
Pharmacokinetics
Drug Discovery
Substrates
Enzymes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Clinical Biochemistry

Cite this

Quantitative evaluation of drug-drug interaction potentials by in vivo information-guided prediction approach. / Chen, Feng; Hu, Zhe Yi; Jia, Wei Wei; Lu, Jing Tao; Zhao, Yuan Sheng.

In: Current Drug Metabolism, Vol. 15, No. 8, 01.01.2014, p. 761-766.

Research output: Contribution to journalArticle

Chen, Feng ; Hu, Zhe Yi ; Jia, Wei Wei ; Lu, Jing Tao ; Zhao, Yuan Sheng. / Quantitative evaluation of drug-drug interaction potentials by in vivo information-guided prediction approach. In: Current Drug Metabolism. 2014 ; Vol. 15, No. 8. pp. 761-766.
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