2014 Fiscal Year Final Research Report
Highthrouput system for detrmination of drug metabolism in cats
| Project/Area Number |
24580462
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Clinical veterinary science
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| Research Institution | Rakuno Gakuen University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
UCHIDE Tsuyoshi 酪農学園大学, 獣医学群, 教授 (20327456)
INOUE Hiroki 酪農学園大学, 農食環境学群, 准教授 (90305904)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 薬物代謝酵素 / シトクロームP450 / コンパニオンアニマル / ネコ / 薬物相互作用 / 中毒 |
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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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| Free Research Field |
獣医薬理学、毒性学
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