Humanized transgenic mouse models for drug metabolism and pharmacokinetic research.
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 drug-metabolizing 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.
Department of Pharmaceutical Sciences University at Buffalo, The State University of New York, 541 Cooke Hall, Buffalo, NY 14260-1200, USA.
Hong-Wu
HW
Shen
Xi-Ling
XL
Jiang
Frank J
FJ
Gonzalez
Ai-Ming
AM
Yu
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D015195:Drug Design; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D001191:Arylamine N-Acetyltransferase; D014453:Glucuronosyltransferase