Drug-Drug Interaction Study Using Triple Humanized Mouse Accepted for Publication by Leading Scientific Journal
News Jul 13, 2011
CXR Biosciences Ltd and Taconic has announced the publication of a collaborative study with the Japanese Pharmaceutical company Kyowa Hakko Kirin, demonstrating that the CXR and Taconic humanized mice can be used to predict drug-drug interactions in humans.
Publication in the prestigious Molecular Pharmacology journal is further confirmation of the enthusiasm in academia and industry for more predictive preclinical models, and further demonstrates how these models can be used to better predict drug exposure, distribution, metabolism and safety in humans.
The paper describes transADMET™ mice humanized for the nuclear receptors PXR & CAR and the cytochrome P450 3A4.
All three are involved in the metabolism of many marketed drugs, and species differences between the human and animal proteins means that studies in conventional animals may not be predictive of man.
The paper, entitled "Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line," demonstrates that the mice can be used to rank PXR ligands according to their potency to induce CYP3A4 expression in the human liver.
Crucially, the mice can also be used to quantitatively predict PXR / CYP3A4-mediated drug-drug interactions in humans.
The hPXR-hCAR-hCYP3A4 mouse is available as part of CXR's and Taconic's transADMET™ program. As for all transADMET™ models, the corresponding murine genes have been replaced with their human counterparts.
transADMET™ humanized and knockout mice are now available for many of the key genes involved in drug metabolism - for instance PXR, CAR, CYP3A4, CYP2D6, CYP2C9 and MDR1.