| Project/Area Number |
26460217
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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 | Kanazawa University |
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Principal Investigator |
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| Research Collaborator |
KOMAI Kiyonobu 国立病院機構医王病院, 院長
ISHIDA Natsuko 国立病院機構金沢医療センター, 主任
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 3,4-diaminopyridine / Lambert-Eaton筋無力症 / bungarotoxin / muscle / pharmacokinetics / pharmacodynamics / LEMS / Lambert-Eaton 筋無力症 / PK-PD / rat |
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| Outline of Final Research Achievements |
3,4-Diaminopyridine (3,4-DAP) is potassium channel inhibitor used to treat Lambert-Eaton myasthenic syndrome (LEMS). We investigated the pharmacokinetics of 3,4-DAP, which are still poorly understood, in rats and humans. In healthy Japanese volunteers, 3,4-DAP Vd/F and T1/2 were varied from 740 to 1669 L and from 35 to51 min, respectively. We found that 3,4-DAP was characterized by fast elimination from serum and high tissue perfusion in a dose-dependent manner. Furthermore, muscle mass was the inter-individual variability factor. In addition, studies in rat tissue distribution and compound muscle action potential with and without alpha-bungarotoxin indicated that 3,4-DAP response delay caused by high muscle distribution compared with plasma disposition.
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