In Vivo Microdialysis for Pharmacokinetic Investigations : A Plasma Protein Binding Study of Valproate in Rabbits
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概要
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The use of microdialysis to study the binding of valproate (VPA) to plasma proteins was evaluated in rabbits. Prior to an in vivo microdialysis, in vitro relative recovery of VPA respectively from Ringer's solution, 5% (w/v) of albumin solution and plasma sample via a microdialysis probe was examined. The in vitro relative recovery was defined as a ratio of the VPA concentration determined in the dialysate to the free VPA concentration in the sample solution surounding the membrane of the microdialysis probe. When the sample solution was well stirred at 700rpm and maintained at 37℃, the in vitro relative recovery of VPA was significantly different among them. It increased in the order of Ringer's solution (34.3±2.6%)>5% (w/v) of albumin solution (25.7±4.6%)> rabbit plasma sample (15.8±1.2%). Thereafter, pharmacokinetics of VPA was determined using both microdialysis sampling via the rabbit femoral vein and collection of whole blood via the rabbit ear vein after intravenous administration of VPA at a dose of 43mg/kg. Free concentrations of VPA in plasma were determined by ultrafiltration method as opposed to microdialysis method. There was no difference in the elimination half-life of VPA determined by microdialysis, 1.09±0.22h, or ultrafiltration, 1.22±0.21h. The AUC of VPA in dialysate was 15±4μg・h/ml, which corresponded to 15% of that in ultrafiltrate (103±17μg・h/ml). The value was in good agreement with the in vitro relative recovery of VPA from plasma sample (15.8±1.2%). On the basis of the obtained recovery of 15.8±1.2%, free VPA in dialysate was corrected to calculated free VPA in plasma, followed by determination of the extent of plasma protein binding of VPA. The extent of plasma protein binding of VPA determined by microdialysis was found to be 69.2±6.9%, which was almost the same as that determined by ultrafiltration (66.6±2.7%). In vivo determination of plasma protein binding of VPA was successfully performed by microdialysis when the in vitro relative recovery of VPA was calculated using plasma sample of the tested animal.
- 社団法人日本薬学会の論文
- 1994-12-15
著者
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市川 正孝
長崎大学医学部附属病院薬剤部
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市川 正孝
ミシガン癌研化学発癌部
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後藤 茂
Faculty Of Pharmaceutical Sciences Kyushu University
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市川 正孝
Department of Hospital Pharmacy, Nagasaki University School of Medicine
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中嶋 幹郎
長崎大学薬剤部
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市川 正孝
Department Of Hospital Pharmacy School Of Medicine Nagasaki University
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松山 賢治
Department of Hospital Pharmacy, School of Medicine, Nagasaki University
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中嶋 幹郎
Department of Hospital Pharmacy, School of Medicine, Nagasaki University
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市川 正孝
長崎大学薬剤部
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竹内 直子
Department of Hospital Pharmacy, School of Medicine, Nagasaki University
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濱田 元子
Department of Hospital Pharmacy, School of Medicine, Nagasaki University
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竹内 直子
Department Of Hospital Pharmacy School Of Medicine Nagasaki University
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松山 賢治
Department Of Hospital Pharmacy School Of Medicine Nagasaki University
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Goto Sigeru
Facultyof Pharmaceutical Sciences Kyushu University
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濱田 元子
Department Of Hospital Pharmacy School Of Medicine Nagasaki University
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後藤 茂
Faculity of Pharmaceutical Sciences, The University of Tokushima
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