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Quantitative Relationship Between Rifampicin Exposure and Induction of CYP3a11 in SXR Humanized Mice: Extrapolation to Human CYP3A4 Induction Potential

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The SXR humanized mouse modle was used to quantitatively assess an vivo induction response of the human PXR agoinst, rifampicin, Three days of rifampicin treatment increased RNA expression and microsomel enzyme activity of CYP3A, as wall as significantly reduced triazolam plasma exposure. These results indicate that the humanized SXR mouse can be used as a modle to prediict human CYP3A4 induction and the resulting pharma cokinetic changes of CYP3A4 substrates in humans.

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Keywords: CYP induction; CYP3A11; CYP3A4; SXR-humanized mouse; drug-drug interaction; rifampicin

Document Type: Research Article

Publication date: August 1, 2008

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  • Drug Metabolism Letters publishes short papers on major advances in all areas of drug metabolism and disposition. The emphasis will be on publishing quality papers very rapidly. Letters will be processed rapidly by taking full advantage of the Internet technology for both the submission and review of manuscripts. The journal covers the following areas:

    In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites, reactive intermediate and glutathione conjugates.
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