2018 Fiscal Year Final Research Report
Appropriate administration of nicotine according to the metabolic enzyme activity estimated from the nicotine metabolites in saliva.
| Project/Area Number |
16K08428
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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 | Hiroshima International University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
杉原 数美 広島国際大学, 薬学部, 教授 (20271067)
谷口 良彦 広島国際大学, 薬学部, 教授 (30403520)
北村 繁幸 日本薬科大学, 薬学部, 客員教授 (40136057)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | nicotine製剤 / 投与設計 |
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| Outline of Final Research Achievements |
1. Semi-quantify system of the concentration of nicotine and their metabolites. We tried to develop a measurement system, it can semi-quantify the concentration of nicotine and the metabolites. Our analysis system was able to be performed up to 10 μg/mL for these compounds by using UV irradiation. 2. The contribution of metabolic enzyme, CYPA6 and AO, on cotinine pharmacokinetics. We used two strains rats with different AO activities and CYP2A6 inhibitors, methoxalene. In inhibition of CYP2A6 activity, it was shown the lower cotinine in serum than no inhibition of CYP2A6. And, low AO rats showed lower cotinine concentration in serum than high AO activity rats. High AO rats with no treatment with methoxalene, (High AO, no inhibiton CYP2A6) showed highest concentration of cotinine in serum among all groups. Not only CYP2A6 but also AO affected on cotinine pharmacokinetics largely. In administration of nicotine, it is necessary to take account for the estimated CYP2A6 and AO activity.
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| Free Research Field |
医療薬学
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| Academic Significance and Societal Importance of the Research Achievements |
禁煙に向けた取り組みとして、禁煙補助薬のニコチン製剤が使用される。この主成分であるnicotineは、cytochrome P-450 2A6 およびaldehyde oxidaseにより代謝される。これら酵素活性には、大きな個体差が存在している。従って、これら酵素の活性を指標としたニコチン製剤の投与設計が望まれる。しかし、これらの酵素活性を推定する機器は、特別な機関に設置してあるのみで、ニコチン製剤を販売している薬局にはない。いずれの施設においてもnicotine代謝酵素活性を測定できる方法を作るとともに、推定した代謝酵素活性より、ニコチン製剤の投与設計を行う簡便な方法をつくりたい。
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