Drug oxygenations and interactions mediated by polymorphic flavin-containing monooxygenases
Project/Area Number |
25460198
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | Showa Pharmaceutical University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Hiroshi 昭和薬科大学, 薬学部, 教授 (30191274)
MURAYAMA Norie 昭和薬科大学, 薬学部, 講師 (90219949)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | フラビン含有酸素添加酵素3 / FMO3 / 薬物代謝酵素 / 相互作用 / フラビン含有酸素添酵素 / 薬物相互作用 / フラビン含有酸素添加酵素 |
Outline of Final Research Achievements |
The flavin-containing monooxygenase 3 (FMO3) catalyzes the oxygenation of N- and S- containing medicines and xenobiotic substances. From viewpoint of growing interest in drug interactions mediated by polymorphic FMO3, benzydamine N-oxygenation and sulindac sulfide S-oxygenation by human liver microsomal FMO3 were investigated as model reactions. Genetic polymorphisms in the human FMO3 gene might lead to some changes of enzyme activities and drug-drug interactions for N- or S-oxygenations of endogenous and xenobiotic substances including medicines. Since even the most common p.[(Glu158Lys; Glu308Gly)] variant FMO3 protein could result in stronger inhibition potential, genetic polymorphism of human FMO3 gene might lead to unexpected drug interactions via modulation of FMO3 catalytic efficiency.
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Activation and deactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by cytochrome P450 enzymes and flavin-containing monooxygenases in common marmosets (Callithrix jacchus).2015
Author(s)
Uehara, S., Uno, Y., Inoue, T., Murayama, N., Shimizu, M., Sasaki, E., and Yamazaki, H.
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Journal Title
Drug Metab. Dispos.
Volume: 43
Issue: 5
Pages: 735-742
DOI
Related Report
Peer Reviewed
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[Journal Article] Oral L-carnitine supplementation increases trimethylamine-N-oxide, but reduces markers of vascular injury in hemodialysis patients.2015
Author(s)
Fukami K, Yamagishi S, Sakai K, Kaida Y, Yokoro M, Ueda S, Wada Y, Takeuchi M, Shimizu M, Yamazaki H, Okuda S.
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Journal Title
J. Cardiovasc. Pharmacol.
Volume: 65.
Issue: 3
Pages: 289-295
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Trimethylamine generation in patients receiving hemodialysis treated with L-carnitine.2014
Author(s)
Ozasa, H., Shimizu, M., Koizumi, A., Wakabayashi, A., Yamazaki, H.
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Journal Title
Clin.Kidney J.,
Volume: 7
Issue: 3
Pages: 329-329
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Effects of ADH1C, ALDH2, and CYP2A6 polymorphisms on individual risk of tobacco-related lung cancer in male Japanese smokers.2013
Author(s)
Shimizu, M., Ishii, Y., Okubo, M., Kunitoh, H., Kamataki, T., and Yamazaki, H.
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Journal Title
J.Cancer Ther
Volume: 4
Issue: 08
Pages: 28-35
DOI
Related Report
Peer Reviewed
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