Leveraging Humanized Animal Models to Understand Human Drug Disposition: Opportunities, Challenges, and Future Directions
Humanized (a.k.a. transgenic) mouse models, where human drug metabolizing enzyme(s) or transporter(s) and/or regulatory elements have replaced the mouse ortholog (knockout/knockin), have recently become commercially available. Their utility to predict and decipher human drug disposition has been investigated. A comprehensive listing of humanized CYP1 and transporter2 mouse models have previously been reviewed and tabulated. We have limited the scope of this commentary to humanized mice; however, rat models have been generated, although not broadly studied/accessible. In addition, chimeric mice, where the liver is repopulated (up to 95%) with human hepatocytes are also available.