title: Can Humanized Mice Predict Drug "Behavior" in Humans?
abstract: Most of what we know about a drug prior to human clinical studies is derived from animal testing. Because animals and humans have substantial differences in their physiology and in their drug metabolism pathways, we do not know very much about the pharmacokinetic and pharmacodynamic behavior of a drug in humans until after it is administered to many people. Hence, drug-induced liver injury has become a significant public health problem, and we have a very inefficient drug development process with a high failure rate. Because the human liver is at the heart of these problems, chimeric mice with humanized livers could be used to address these issues. We examine recent evidence indicating that drug testing in chimeric mice could provide better information about a drug's metabolism, disposition, and toxicity (i.e., its "behavior") in humans and could aid in developing personalized medicine strategies, which would improve drug efficacy and safety.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305; email: gpeltz@stanford.edu.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305; email: gpeltz@stanford.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Peltz
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000517:prevention & control*; D002678:Chimera / Q000502:physiology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008099:Liver / Q000187:drug effects*; D051379:Mice
keywords: chimeric mice; drug metabolism; liver humanization; predictive toxicology