| Project/Area Number |
02670459
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Kitasato University |
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Principal Investigator |
MIURA Hisao M.D. Kitasato University School of Medicine, Professor., 医学部, 教授 (60050465)
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| Co-Investigator(Kenkyū-buntansha) |
ABO Ken-ichi Abo, M.D., 医学部, 助手 (80202688)
細田 のぞみ 北里大学, 医学部, 助手 (80199504)
SUNAOSHI Wataru M.D., Nozomi Hosoda, M.D.,, 医学部, 講師 (20171283)
白井 宏幸 北里大学, 医学部, 講師 (10154353)
TAKANASHI Sakae M.D., Hiroyuki Shirai, M.D.,, 医学部, 講師 (40146436)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Antiepileptic drug / Pharmacokinetics / Drug interaction / Carbamazepine / Carbamazepine metabolite / Valproic acid / Epilepsy / Zonisamide / 薬物血中濃度 / 血中濃度 / 部分発作 / バルプロ酸ナトリウム |
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| Research Abstract |
1. The influence of concurrently administered sodium valproate (VPA) on the steady-state plasma concentrations of carbamazepine (CBZ), carbamazepine-10, 11-epoxide (CBZ-E) and its diol metabolite 10, 11-dihydroxycarbamazepine (CBZ-H) was investigated in patients receiving CBZ together with VPA, who received no other anticonvulsants. CBZ is extensively metabolized to the active metabolite CBZ-E and finally to the inactive CBZ-H.
Our study showed that the plasma levels of CBZ-E and CBZ-E/CBZ ratio were significantly higher in the patients treated concurrently with CBZ and VPA than in those treated with CBZ alone, whereas the plasma CBZ-H/CBZ-E ratio was significantly lower in the former group.
It was shown also that the concurrent administration of VPA raises the free fraction of both CBZ and CBZ-E. Consequently, a simultaneous administration of VPA increases the total plasma CBZ-E level relative to the CBZ dose, associated with the raised free fraction of CBZ and CBZ-E. The high plasma co
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ncentration of CBZ-E may be responsible for the side effects in some patients.
2. The clinical effects and plasma levels of zonisamide (ZNS) were investigated in children with cryptogenic localization-related epilepsies, who were administered ZNS once a day as a single drug. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long compared with the other prevalent antiepileptic drugs. Blood samples for determination of plasma levels were taken before and 4 hours after the morning dose, each of which represents the trough and peak levels in a day.
The peak to trough plasma level ratios were as small as approximately 1.25. The plasma level (mug/m) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels increased both with advance in age. The clinical effects in the patients were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, that is 15-40mug/ml.
The concurrent administration of CBZ decreased the plasma concentrations of ZNS in most of the patients, whose seizures were not controlled by once-daily dose of ZNS monotherapy, in spite of maintaining the high plasma levels. Less
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