Transport and distribution space of niflumic acid in the perfused rat liver were investigated employing the multiple-indicator dilution technique with constant infusion of the drug (step input). Niflumic acid permeated the cell membrane in both directions at very high rates and its distribution in the cellular space was flow-limited; at least at 37 degrees, the rates of influx and efflux could not be measured. Dissociation of the niflumic acid-albumin complex also occurred at very high rates. The apparent space of distribution of niflumic acid in the liver depended on the concentration of the drug and varied between 4.37 (1 mM) and 43.5 (10 microM) times the water space; even with 90% extracellular binding to albumin, the apparent space of distribution of niflumic acid was 5.1 times greater than the water space. The high apparent spaces of distribution reflected the high intracellular concentrations. The ratio of intracellular bound plus free concentration to the extracellular bound plus free concentration (Ci/Ce) varied between 6.62 (1 mM portal niflumic acid) and 71.0 (10 microM portal niflumic acid). Metabolic transformation depended on the concentration of the free form. Intracellular binding is probably the major reason for the high concentration of the drug in the hepatic tissue.

中文翻译：

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灌注大鼠肝脏中抗炎药尼氟酸的转运，分布空间和细胞内浓度。

采用多指标稀释技术并持续输注药物，研究了灌注大鼠肝中尼氟酸的转运和分布空间。尼氟酸以很高的速率沿两个方向渗透细胞膜，并且其在细胞空间中的分布受到限制。至少在37度时，无法测量流入和流出的速率。尼氟酸-白蛋白复合物的解离也以很高的速率发生。尼氟酸在肝脏中的表观分布空间取决于药物的浓度，在水空间的4.37（1 mM）和43.5（10 microM）倍之间变化。即使90％的细胞外结合白蛋白，尼氟酸的表观分布空间也比水空间大5.1倍。高的表观分布空间反映了高的细胞内浓度。细胞内结合加游离浓度与细胞外结合加游离浓度（Ci / Ce）之比在6.62（1 mM门尼氟酸）和71.0（10 microM门尼氟酸）之间变化。代谢转化取决于游离形式的浓度。细胞内结合可能是药物在肝组织中高浓度的主要原因。