2016 Fiscal Year Final Research Report
The functional chacterization of marmoset cytochrome P450 2C enzymes
| Project/Area Number |
15K18934
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
Uehara Shotaro 昭和薬科大学, 薬学部, 特任助教 (10733123)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMAZAKI Hiroshi 昭和薬科大学, 薬物動態学研究室, 教授 (30191274)
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| Research Collaborator |
UNO Yasuhiro 株式会社新日本科学
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | チトクロムP450 / マーモセット |
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| Outline of Final Research Achievements |
The enzymatic function of marmoset cytochrome P450 2C enzymes was analyzed. Recombinant marmoset P450 2C19 effectively metabolized human P450 2C substrates, S-warfarin, diclofenac, tolbutamide, flurbiprofen, and omeprazole. Marmoset P450 2C19 had high capacity and affinity for S-warfarin 7-hydroxylation that were comparable to those in human liver microsomes, indicating warfarin stereoselectivity similar to findings in humans. The interindividual variability of P450 2C-dependent drug metabolism such as S-warfarin clearance is at least partly accounted for by P450 2C19 variants p.[(Phe7Leu; Ser254Leu; Ile469Thr)] in marmosets. These findings on inter-individual variability and substrate specificity of marmoset P450 enzymes should help to understand apparent species differences in drug metabolism and disposition among marmosets and humans and to extrapolate the preclinical study data obtained using marmosets to humans.
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| Free Research Field |
薬物代謝
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