2014 Fiscal Year Final Research Report
The most suitable administration of antidepressive drug to avoid risk of side effects in patient
| Project/Area Number |
24590211
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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 |
Medical pharmacy
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| Research Institution | Showa Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Hiroshi 昭和薬科大学, 薬学部, 教授 (30191274)
SHIMIZU Makiko 昭和薬科大学, 薬学部, 講師 (90307075)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | P450 / 向精神薬 / 相互作用 / 酵素誘導 / 遺伝子多型 / CYP3A5 |
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| Outline of Final Research Achievements |
The plasma concentrations of mirtzapine in patients are influenced by many factors, such as polymorphic cytochrome P450 enzymes contributing to its transformation to the metabolites.The aim of this study was to investigate the determinant factors for individual variations of metabolic clearance of mirtazapine using in vitro and in vivo methods. The plasma concentration/dose ratios of mirtazapine from 14 patients were significantly higher in the CYP2D6 IM/PM group than in the EM group and were also higher in the CYP3A5 poor-expressors group than in the expressors group (p<0.05). In vitro, mirtazapine 8-hydroxylation activities in individual liver microsomes were significantly lower in CYP2D6 intermediate metabolizers (IM) and poor metabolizers (PM) than in extensive metabolizers (EM) (p<0.05).These results suggested that mirtazapine metabolic clearance could be variously influenced by the CYP2D6 and CYP3A5 genotypes and coadministered drugs in clinical patients.
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| Free Research Field |
薬物代謝
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