Humanization of Excretory Pathway in Chimeric Mice with Humanized Liver
نویسندگان
چکیده
منابع مشابه
In vivo induction of human cytochrome P450 enzymes expressed in chimeric mice with humanized liver.
The induction and inhibition of human cytochrome P450 (P450) enzymes are clinically responsible for drug interactions. Although the induction of P450s is investigated using human hepatocytes in the drug development process, there are some disadvantages, such as the decline of the enzyme activity during culture. In the present study, we examined the in vivo induction potency in chimeric mice wit...
متن کاملExpression of human cytochromes P450 in chimeric mice with humanized liver.
Recently, a chimeric mouse line in which the liver could be replaced by more than 80% with human hepatocytes was established in Japan. Because the chimeric mouse produces human albumin (hAlb), replacement by human hepatocytes could be estimated by the hAlb concentration in the blood of chimeric mice. In this study, we investigated human major cytochrome P450 (P450) in the livers of chimeric mic...
متن کاملExpression of human phase II enzymes in chimeric mice with humanized liver.
We clarified that major human cytochrome P450 (P450) enzymes were expressed in a chimeric mouse line established recently in Japan, in which the liver could be replaced by more than 80% with human hepatocytes. In this study, we investigated major human phase II enzymes such as UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), N-acetyltransferase (NAT), and glutathione S-transferase (G...
متن کاملApplication of chimeric mice with humanized liver for study of human-specific drug metabolism.
Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively asse...
متن کاملAssessment of chimeric mice with humanized liver as a tool for predicting circulating human metabolites.
The ability to predict circulating human metabolites of a candidate drug before first-in-man studies are carried out would provide a clear advantage in drug development. A recent report demonstrated that while in vitro studies using human liver preparations reliably predict primary human metabolites in plasma, the predictability of secondary metabolites, formed by multiple reactions, was low, w...
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ژورنال
عنوان ژورنال: Toxicological Sciences
سال: 2007
ISSN: 1096-6080,1096-0929
DOI: 10.1093/toxsci/kfm041