In Vivo Microdialysis to Determine the Relative Pharmacokinetics of Drugs
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概要
- 論文の詳細を見る
The purpose of this study was to evaluate a simultaneous microdialysis method in blood and brain striatum to determine the relative pharmacokinetics and matabolism of L-3,4-dihydroxyphenylalanine (L-dopa). L-Dopa (250 μmol/kg) was administered to rats with or without the aromatic amino acid decarboxylase (AADC) inhibitor carbidopa (25 μmol/kg) or benserazide (25 or 62.5 μmol/kg). L-Dopa, its metabolites, and AADC inhibitors in dialysates were analyzed by high performance liquid chromatography with an electrochemical detector. A moment analysis was also made to obtain pharmacokinetic parameters.After administration of L-dopa alone, it and its related metabolites were detected in both dialysates of blood and brain striatum. Coadministration of carbidopa (25 μmol/kg) or benserazide (62.5 μmol/kg) significantly enhanced the striatal amount of L-dopa by 8.0 and 6.1 times, respectively. Carbidopa and benserazide also increased striatal amounts of L-dopa metabolites, such as 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol. Inhibition effect of benserazide on an extracerebral decarboxylation of L-dopa to dopamine (DA) was stronger than that of carbidopa. Carbidopa showed a higher striatal level of DA than benserazide. These results suggest a different effect of the two inhibitors on the DA formations in blood and brain striatum, and on the L-dopa transport through the blood-brain barrier (BBB).Thus, microdialysis is an easy and available method for simultaneously assessing the in vivo relative pharmacokinetics and metabolism of drugs in systemic circulation and a target organ.
- 公益社団法人日本薬学会の論文
- 1996-07-15
著者
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中島 幹夫
佐賀大学医学部附属病院 手術部
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NAKASHIMA Mikiro
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry
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SASAKI Hitoshi
Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry
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Nakashima Mikiro
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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Sasaki H
Dep. Of Hospital Pharmacy Nagasaki Univ. Hospital
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ICHIKAWA Masataka
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University
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Sasaki Hitoshi
長崎大学 医歯学部病院薬剤部
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Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
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Matsuyama Kenji
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Mukogawa Women's University
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NAKASHIMA Mihoko
Department of Analytical Research for Pharmacoinformatics, Graduate School of Pharmaceutical Science
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Matsuyama Kenji
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Mukogawa Women's University
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ZHAO Mei
Department of Hospital Pharmacy, Nagasaki University School of Medicine
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SAKURAI Masaharu
Department of Hospital Pharmacy, Nagasaki University School of Medicine
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Zhao Mei
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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Ichikawa Masataka
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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Ichikawa Masataka
Department Of Pharmacy Nagasaki University Hospital
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Sakurai Masaharu
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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Sakurai Masaharu
Department Of Hospital Pharmacy Nagasaki University Hospital
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Nakashima Mihoko
Department Of Analytical Research For Pharmacoinformatics Graduate School Of Pharmaceutical Sciences
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Matsuyama Kenji
Department Of Hospital Pharmacy Nagasaki University School Of Medicine
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ICHIKAWA MASATAKA
Department of Hospital Pharmacy, Nagasaki University School of Medicine
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Nakashima Mikiro
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
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ICHIKAWA MASATAKA
Department of Chemical Engineering, Kyushu University
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