Pharmacokinetic and Pharmacodynamic Studies of L-Dopa in Rats. I. Pharmacokinetic Analysis of L-Dopa in Rat Plasma and Striatum
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概要
- 論文の詳細を見る
The purpose of this investigation was to quantitatively describe the pharmacokinetics of exogenous and endogenous L-dopa in plasma and the striatum using a basic physiological model, and to determine the apparent metabolism clearance from L-dopa to dopamine in the striatum. Male Wistar rats were used in this study. The time courses of L-dopa concentrations in plasma and the striatum were determined before and after the rapid i. v. injection of 10,50 and 100mg/kg. Plasma and striatum samples were obtained over 480min (17 time points) from different group of animals and the assayed by HPLC-ECD. The endogenous L-dopa concentration in plasma before drug administration was 2.1±0.6mg/I. The exogenous L-dopa concentration declined biexponentially with time after drug injection. The total clearance of exogenous L-dopa in plasma was 3.13 (I/h)/kg. The production rate constant of endogenous L-dopa in plasma was 6.59 (mg/h)/kg. The value of the production rate constant of endogenous L-dopa in plasma could be calculated by the multiplication of the total clearance of L-dopa and the endogenous L-dopa concentration in plasma before drug injection. The pharmacokinetics of endogenous and exogenous L-dopa in plasma could be described quantitatively by a two compartment model which included the production rate constant of endogenous L-dopa. The time course of L-dopa concentrations in the striatum was analyzed on a hybrid model in which the striatum compartment is independently connected with the plasma compartment by the apparent diffusion clearance. The striatum compartment has two apparent first-order clearance terms, one from the plasma to the striatum, the other from the striatum to the outside of the striatum, including the metabolism clearance from L-dopa to dopamine in the striatum. The time course of L-dopa concentration in the striatum could be described by the basic physiological model, and the apparent metabolism clearance from L-dopa to dopamine in the striatum could be determined by the basic physiological model.
- 社団法人日本薬学会の論文
- 1994-12-15
著者
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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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佐藤 眞治
新潟薬科大学
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佐藤 眞治
Department of Pharmaceutics, Niigata College of Pharmacy
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小板橋 敏信
Department of Pharmaceutics, Niigata College of Pharmacy
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Koshiro Akira
Department Of Pharmaceutics Niigata College Of Pharmacy
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Koitabashi T
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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佐藤 眞治
Pharmaceutical Research Laboratories Ajinomoto Co. Inc.
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小板橋 敏信
Department Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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小板橋 敏信
Department Of Pharmaceutics Niigata College Of Pharmacy
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Sato Shinji
Department Of Pharmaceutics Niigata College Of Pharmacy
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