Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

摘要: Abstract Predicting human drug metabolism and pharmacokinetics (PK) is key to discovery. In particular, it important predict PK, metabolite profiles drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using biological samples, as hepatic microsomes hepatocytes, in vivo experimental animals. However, prediction these are often inconclusive due discrepancies between results, interspecies differences in metabolism. Further, the changed from qualitative quantitative solve issues. Chimeric mice with humanized liver developed, which mouse cells mostly replaced hepatocytes. Since metabolizing enzymes expressed of mice, they regarded suitable models mimicking PK observed humans; therefore, useful predicting PK. this review, we discuss current state, issues, future directions chimeric