Humanized transgenic mouse models for drug metabolism and pharmacokinetic research

Hong Wu Shen, Xi Ling Jiang, Frank J. Gonzalez, Aiming Yu

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Extrapolation of the metabolic, pharmacokinetic and toxicological data obtained from animals to humans is not always straightforward, given the remarkable species difference in drug metabolism that is due in large part to the differences in drugmetabolizing enzymes between animals and humans. Furthermore, genetic variations in drug-metabolizing enzymes may significantly alter pharmacokinetics, drug efficacy and safety. Thus, humanized transgenic mouse lines, in which the human drug-metabolizing enzymes are expressed in mouse tissues in the presence or absence of mouse orthologues, have been developed to address such challenges. These humanized transgenic mice are valuable animal models in understanding the significance of specific human drug-metabolizing enzymes in drug clearance and pharmacokinetics, as well as in predicting potential drug-drug interactions and chemical toxicity in humans. This review, therefore, aims to summarize the development and application of some humanized transgenic mouse models expressing human drug-metabolizing enzymes. The limitations of these genetically modified mouse models are also discussed.

Original languageEnglish (US)
Pages (from-to)997-1006
Number of pages10
JournalCurrent Drug Metabolism
Volume12
Issue number10
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • Cancer
  • Drug interaction
  • Drug metabolism
  • Humanized
  • Mouse model
  • Pharmacokinetics
  • Toxicity
  • Transgenic

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

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