Harashima H, Mamiya M, Yamazaki M, Sawada Y, Iga T, Hanano M, Sugiyama Y
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Pharm Res. 1992 Dec;9(12):1607-11. doi: 10.1023/a:1015820610048.
The significance of the binding to Na,K-ATPase in the tissue distribution of ouabain was previously documented (Harashima et al., Pharm. Res. 9:474-479, 1992). The purpose of this study was to obtain a kinetic model of ouabain tissue distribution. In most tissues, the ouabain concentration continued to rise after the termination of infusion (5 min), with the peak tissue concentration at approximately 20 min. This delay could not be explained by the rapid equilibrium model (RE model), nor could the kinetics of ouabain be explained by an RE model modified for saturable binding. Since ouabain binding to Na,K-ATPase is slow, the association and dissociation processes were incorporated into a model that can accurately fit the observed time courses of ouabain. The obtained binding parameters corresponded well with the observed values in the in vitro binding experiments, except for muscle. These results quantitatively support the role of the slow and saturable binding of ouabain to Na,K-ATPase in its tissue distribution.
哇巴因在组织分布中与钠钾 - ATP酶结合的重要性先前已有文献记载（原岛等人，《药物研究》9:474 - 479，1992年）。本研究的目的是获得哇巴因组织分布的动力学模型。在大多数组织中，输注终止（5分钟）后哇巴因浓度持续上升，组织浓度峰值约在20分钟时出现。这种延迟无法用快速平衡模型（RE模型）解释，为可饱和结合而修正的RE模型也无法解释哇巴因的动力学。由于哇巴因与钠钾 - ATP酶的结合缓慢，将结合和解离过程纳入一个能够准确拟合观察到的哇巴因时间进程的模型中。除肌肉外，所获得的结合参数与体外结合实验中的观察值相当吻合。这些结果定量地支持了哇巴因与钠钾 - ATP酶的缓慢且可饱和结合在其组织分布中的作用。
