AGE-DEPENDENT CHANGES IN PHENYTOIN TISSUE BINDINGS IN RATS : COMPARISON BETWEEN IN VIVO AND IN VITRO TISSUE-TO-BLOOD PARTITION COEFFICIENTS (K_p VALUES) OF PHENYTOIN
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概要
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Age-dependent changes in phenytoin tissue bindings in rats were investigated by equilibrium dialysis using serum and 10% tissue (brain, lung, liver, kidney and muscle) homogenates. All percentages of phenytoin bound to serum and tissue homogenates were independent of the initial phenytoin concentration (2 to 25 μg/ml) in 1-d, 1-, 3- and 8-week-old rats. The percentages bound to serum, brain, liver, kidney and muscle in newborn rats (1-d-old rats) were lower than those in 8-week-old rats and the percentages bound increased gradually in the growth process. However, those in lungs were constant in all ages of rats. It was assumed that the age-dependent changes in phenytoin tissue binding were caused by the changes in the quantities of tissue constituents to which phenytoin bound in the growth process. Tissue-to-blood partition coefficients (K_p values) were calculated from in vitro tissue binding data and the pH-difference across the cell membrane. These K_p values were in good agreement with the in vivo K_p values reported previously. It was concluded that the age-dependent changes in phenytoin tissue distribution were caused by the age-dependent changes in phenytoin binding to blood constituents and tissues but that the change of phenytoin blood binding contributed to the age-dependent changes in K_p values of phenytoin more than to phenytoin tissue binding and consequently the K_p values of phenytoin decreased as rats grew.
- 公益社団法人日本薬学会の論文
著者
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Kato Yoshihisa
School Of Pharmaceutical Science University Of Shizuoka
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HORIKOSHI Isamu
Department of Hospital Pharmacy Toyama Medical and Pharmaceutical University
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Sakaguchi Kazuo
Department Of Hospital Pharmacy Toyama Medical And Pharmaceutical University
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Ueno Masaharu
Department Of Hospital Pharmacy Toyama Medical And Pharmaceutical University
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KATO Yoshiteru
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University
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HIRATE Junji
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University
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Hirate J
Department Of Hospital Pharmacy Toyama Medical And Pharmaceutical University
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Hirate Junji
Department Of Hospital Pharmacy Toyama Medical And Pharmaceutical University
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Kato Y
Yoshitomi Pharmaceutical Industries Ltd. Fukuoka Jpn
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Kato Yoshiteru
Department Of Biopharmaceutics Tokyo College Of Pharmacy
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Kato Yoshiteru
Formulation Research Lab. Kawashima Industrial Park Eisai
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Horikoshi I
Toyama Medical And Pharmaceutical Univ. Toyama Jpn
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Ueno Masaharu
Department Of Chemistry School Of Science And Graduate School Of Pharmaceutical Sciences The Univers
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