In vivo drug metabolism model for human cytochrome P450 enzyme using chimeric mice with humanized liver.

@article{Katoh2007InVD,
  title={In vivo drug metabolism model for human cytochrome P450 enzyme using chimeric mice with humanized liver.},
  author={M. Katoh and T. Sawada and Y. Soeno and M. Nakajima and C. Tateno and K. Yoshizato and T. Yokoi},
  journal={Journal of pharmaceutical sciences},
  year={2007},
  volume={96 2},
  pages={
          428-37
        }
}
We previously clarified that major human drug metabolizing enzymes were expressed in a chimeric urokinase-type plasminogen activator (uPA)+/+/severe combined immunodeficient (SCID) mouse line established recently, in which the liver could be replaced by more than 80% with human hepatocytes. In the present study, we investigated the in vivo drug metabolism of a CYP2D6 substrate, debrisoquin (DB), in chimeric mice with high (High) or low (Low) human albumin (hAlb) concentrations and in control… Expand
Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver
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TLDR
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TLDR
These humanized mouse models will likely be quite valuable for investigations of human liver-mediated metabolism and excretion of drugs and xenobiotics, drug-drug interactions, and for short- and long-term investigation of the toxicity of drugs or chemicals with significant human exposure. Expand
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TLDR
It is concluded that chimeric mice may be a useful tool for supplying fresh h-hepatocytes on demand that provide high and stable phase I enzyme and glucuronidation activities. Expand
Chimeric mice with humanized liver.
TLDR
It was indicated that the chimeric mice could be useful for assessing drug interactions in vivo and overcome the species differences in drug metabolism and be used to evaluate drug toxicity due to genetic polymorphism. Expand
Application of Chimeric Mice with Humanized Liver for Study of Human-Specific Drug Metabolism
TLDR
The data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation. Expand
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TLDR
The current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery are discussed. Expand
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TLDR
This model is closer to in vivo human physiology and therefore appears to have an advantage over in vitro systems in predicting complex metabolites in human plasma, however, prediction of human metabolites failed for other compounds which were highly metabolized in mice. Expand
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It was demonstrated that human P450s expressed in the chimeric mice with humanized liver were induced by rifampicin and 3-MC, and this chimeric mouse model may be a useful animal model to estimate and predict the in vivo induction of P 450s in humans. Expand
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It was demonstrated thathuman CYP3A4 expressed in the chimeric mice with humanized liver was induced by rifabutin, suggesting that human CYP 3A4 in the Chimeric mice had induction potency. Expand
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