Pharmacokinetic and Pharmacodynamic Studies of Centrally Acting Drugs in Rat : Effect of Pentobarbital and Chlorpromazine on Electroencephalogram in Rat
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概要
- 論文の詳細を見る
Electroencephalogram (EEG) alterations in rat after the i.v. administration of pentobarbital (PTB) and chlorpromazine (CPZ) were measured by power spectral analysis. The time courses of PTB concentrations in plasma, cerebrospinal fluid (CSF) and brain were determined after the i.v. administration of PTB (20,40mg/kg) by GC-MS. The PTB concentrations in plasma, CSF and brain could be described by a biexponential equation, a CSF model and a blood flow limited model, respectively. The relationship between the alteration of EEG and the PTB concentrations in the CSF or brain or the effect compartment were analyzed using the sigmoid E_<max> model. The alteration of EEG after PTB administration could be described by the PTB concentration in these compartments using the sigmoid E_<max> model. These results indicated that the site of action for the alteration of EEG after PTB administration is in instantaneous equilibrium with the CSF, the brain and the effect compartment. Thus, alterations in EEG after PTB administration can be predicted by monitoring the total PTB concentration in plasma. The alteration of EEG after i.v. administration of CPZ (4mg/kg) showed a two-phase variation. Although the relationship between the alteration of EEG and the CPZ concentrations in CSF or the striatum or the effect compartment (total and free drug) were analyzed using the linear model, the E_<max> model or the sigmoid E_<max> model, the two-phase alteration of EEG after CPZ administration could not be described by any of these models. These results indicated that the pharmacokinetic and pharmacodynamic modeling of CPZ during the alteration of EEG may be complicated due to several pharmacokinetic and pharmacodynamic factors, such as an alteration of the free fraction of CPZ in the striatum, the formation of active metabolites, and two different intrinsic effects of CPZ on the EEG (one in an increase and the other in a decrease of the brain's electrical activity).
- 社団法人日本薬学会の論文
- 1995-08-15
著者
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小泉 保
富山医科薬科大学
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片山 和憲
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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小泉 保
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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佐藤 眞治
新潟薬科大学薬剤学教室
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佐藤 真治
新潟薬科大学 薬理
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神代 昭
Department Of Pharmaceutics Niigata College Of Pharmacy
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片山 和憲
富山医薬大薬
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佐藤 眞治
新潟薬科大学
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小泉 保
富山医科薬科大学薬学部
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小泉 保
Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University
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Kakemi M
Department Of Biopharmaceutics Osaka University Of Pharmaceutical Science
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掛見 正郎
Department Of Biopharmaceutics Osaka University Of Pharmaceutical Science
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Katayama Kazunori
Faculty Of Pharmaceutical Science Toyama Medical And Pharmaceutical University
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Koizumi Tamotsu
Faculty Of Pharmaceutical Science Toyama Medical And Pharmaceutical University
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Kawasaki M
Department Of Biological Pharmaceutical Sciences College Of Pharmacy Nihon-university
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佐藤 眞治
Department of Pharmaceutics, Niigata College of Pharmacy
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深沢 芳樹
Faculty of Pharmaceutical Science, Toyama Medical and Pharmaceutical University
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Koshiro Akira
Department Of Pharmaceutics Niigata College Of Pharmacy
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佐藤 眞治
Pharmaceutical Research Laboratories Ajinomoto Co. Inc.
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深沢 芳樹
Faculty Of Pharmaceutical Science Toyama Medical And Pharmaceutical University
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掛見 正郎
Department of Biological Pharmaceutical Sciences, College of Pharmacy, Nihon-University
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