Muscle Microdialysis as a Model Study to Relate the Drug Concentration in Tissue Interstitial Fluid and Dialysate
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概要
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The steady-state dialysis kinetics in buffer, erythrocyte suspension and muscle have been analyzed by clearance theory in the microdialysis study. "Tube"model has been demonstrated to be a useful model to relate the dialysis clearance, CL_D, the dialysis flow rate, F, and the permeability rate constant, PA, for microdialysis employing the transcranial type microdialysis probe. The effective dialysis coefficient (R_d), defined as the ratio of the in vivo PA and in vitro PA, was introduced to account for the differences between in vivo and in vitro microdialyses. The Arrhenius plot of the antipyrine permeability rate constant presented a single straight line in the range of 15-37℃ with an activation energy of 5.49 kcal/mol. A fairly good correlation was observed between the reciprocal of the permeability rate constant and the root of the molecular weight in the range of 18-1039. On the contrary, the molecular weight and the plasma membrane permeability were not determinant factors for R_d value determined in the erythrocyte suspension (R_<d, erythrocyte>), while the interstitial fluid space (100-hematocrit)% of erythrocyte suspension plays a dominant factor to change R_<d, erythrocyte>. The in vivo permeability rate constant was determined in the muscle for [^3H] water, [^<14>C] urea, antipyrine and [^<14>C] sucrose under the steady-state condition. No significant difference of R_d in muscle tissue was demonstrated for these four model substances. By using the R_d value, a hypothetical equation has been proposed to relate the concentration in the dialysate and the interstitial fluid at steady-state.
- 公益社団法人日本薬学会の論文
著者
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Tsuji Akira
金沢大学 薬
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Tsuji Akira
富山化学工業綜合研究所
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Tsuji A
Kanazawa Univ. Ishikawa Jpn
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TERASAKI Tetsuya
Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku
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Tsuji Akira
Department Of Pediatrics:hospital Pharmacy:and Faculty Of Pharmaceutical Sciences University Of Kana
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DEGUCHI Yoshiharu
Department of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka
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Terasaki Tetsuya
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Kanazawa University
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Terasaki Tetsuya
Department Of Molecular Biopharmacy And Genetics Graduate School Of Pharmaceutical Sciences Tohoku U
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出口 芳春
School Of Pharmaceutical Sciences Teikyo University
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Tsuji Akira
Department Of Molecular Pharmaceutics Graduate School Of Natural Science And Technology Kanazawa Uni
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Deguchi Y
School Of Pharmaceutical Sciences Teikyo University
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KAWASAKI Sachiko
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kanazawa University
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Terasaki T
Kanazawa Univ. Kanazawa Jpn
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Deguchi Yoshiharu
Department Of Pharmaceutics Faculty Of Pharmaceutical Sciences Kanazawa University
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Kawasaki Sachiko
Faculty Of Pharmaceutical Sciences Kanazawa University
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