| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
Cytochrome P450s (CYPs) are most important metabolizing enzymes for pharmaceutical drugs in mammals. Although domestic cat is the most common companion animal, the properties of the CYPs are largely unknown. In this study, we developed heterologously expressed feline CYPs in Escherichia coli to generate high-throughput CYPs activity assay systems. CYP2E2 transcripts were most abundant followed by 2A13 in the liver, while CYP3A131 is the major CYP in the small intestine. Suitable fluorescent substrate for high-throuput screening was selected for each CYP subtype. Some antifungal agents and sadatives showed strong inhibition in CYP subtype-specific manner. We could not find any drug that inhibits CYP2E2 in lower concentration. Many drugs inhibited CYP3A131 in relatively higher concentrations than human CYP3A4 and canine CYP3A12. The results suggest the usefulness of this system.
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