| Project/Area Number |
61570467
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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 Kitasato University School of Medicine, Professor, 医学部, 教授 (60050465)
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| Co-Investigator(Kenkyū-buntansha) |
SUNAOSHI Wataru Kitasato University School of Medicine, Research Associate, 医学部, 助手 (20171283)
SHIRAI Hiroyuki Kitasato University School of Medicine, Research Associate, 医学部, 助手 (10154353)
MIZUNO Satoshi Kitasato University School of Medicine, Acting Professor, 医学部, 講師(非常勤) (50146437)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Antiepileptic drug / Clinical pharmacology / Drug interaction / Plasma level / Carbamazepine / Carbamazepine-10,11-epoxide / Clonazepam / sodium valproate / sodium ralproate |
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| Research Abstract |
During the past 10 years, better results in the treatment of epilepsy have been obtained through the application of pharmacokinetic data to drug therapy of epilepsy. However, pediatric drug therapy is complicated by the continuous change in body weight and body composition with the growth and development.
The plasma levels and seizure control were investigated in a prospective randomized stury when phenytion, carbamazepine (CBz) or sodium valproate (VPA) was given as a single drug to pediatric patients with several types of epileptic seizures. Studies on newly referred, previously untreated children suggest that both partial and generalized tonic-clonic seizured can be prevented by each of the three drugs. No significant differences in clinical efficacy were found between the three drugs, when optimum plasma concentration ranges were maintained with blood level monitoring.
Clonazepan (CZP) may be effective in partial seizures. However, as a wide range of plasma levels was associated with complete freedom from seizures, it was not possible to define a therageutic range for CZP.
Any patient who receives multiple-drug therapy is at risk to develop a drug-drug interaction. Simultaneous administration of VPA was associated with a raised plasma level of carbamazepine-10,11-eposiex (CBZ-E), a major metabolite of CBZ, relative to the CBZ dose, whereas the plasma CBZ level remained unaltered. The high plasma concentration of CBZ-E may be responsible for the side-effects in some patients.
Drug-protein binding interactions are another source of side-effects. The unbound or protein-free plasma levels of both CBZ and CBZ-E in patients treated with CBZ and VPA were significantly higher than those in patients treated with CBZ alone.
A working knowledge of the pharmacokinetic principles is an important basis for treating children with antiepileptic drugs.
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