Kelmer-Bracht A M, Ishii-Iwamoto E L, Bracht A
Laboratory of Liver Metabolism, University of Maringá, Brazil.
Res Commun Mol Pathol Pharmacol. 1995 Sep;89(3):411-9.
Intracellular binding of niflumic acid in the perfused rat liver was analyzed according to the model of Scatchard. The data for the binding isotherm were obtained from previously published indicator dilution experiments. The intracellular bound niflumic acid was calculated as the difference between total concentration and the concentration of the free form. The intracellular concentration of the free form was inferred from the concentration of the free form in the extracellular space under the assumption of equilibrative distribution. A Scatchard model with two classes of binding sites fits very well to the experimental curve. The high affinity class has a dissociation constant of 26.10 +/- 0.69 microM and a maximal binding capacity of 2.21 +/- 0.03 micromol (ml intracellular space)(-1); the low affinity class has a dissociation constant of 721.90 +/- 229.0 microM and a maximal binding capacity of 5.96 +/- 0.67 micromol (ml intracellular space)(-1). Probably, under in vivo conditions, the binding capacity in the cellular space exceeds that of the extracellular space. This phenomenon explains, partly at least, the high intracellular concentrations of niflumic acid found under in vivo conditions.
根据Scatchard模型分析了灌注大鼠肝脏中尼氟灭酸的细胞内结合情况。结合等温线的数据取自先前发表的指示剂稀释实验。细胞内结合的尼氟灭酸通过总浓度与游离形式浓度之差计算得出。游离形式的细胞内浓度是在平衡分布的假设下，根据细胞外空间中游离形式的浓度推断出来的。具有两类结合位点的Scatchard模型与实验曲线拟合得非常好。高亲和力类别具有26.10±0.69微摩尔的解离常数和2.21±0.03微摩尔（每毫升细胞内空间）的最大结合容量；低亲和力类别具有721.90±229.0微摩尔的解离常数和5.96±0.67微摩尔（每毫升细胞内空间）的最大结合容量。在体内条件下，细胞空间中的结合容量可能超过细胞外空间。这种现象至少部分解释了在体内条件下发现的高细胞内尼氟灭酸浓度。
