Imamura Y, Abe H, Kojima Y, Otagiri M
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
J Pharmacobiodyn. 1989 Aug;12(8):503-7. doi: 10.1248/bpb1978.12.503.
The in vivo and in vitro bindings of (-)-hydroxyhexamide, a major metabolite of acetohexamide, to rabbit serum were examined by using an ultrafiltration method. The in vivo serum protein binding of (-)-hydroxyhexamide was much lower than the in vitro serum protein binding. The in vitro serum protein binding of (-)-hydroxyhexamide was strongly displaced by the addition of acetohexamide. Furthermore, the in vitro serum protein binding of (-)-hydroxyhexamide in the presence of acetohexamide and (-)-hydroxyhexamide at the same concentrations as those found 1.0 h after acetohexamide administration was approximately similar to the in vivo serum protein binding of (-)-hydroxyhexamide. These results lead us to conclude that acetohexamide, the parent drug of (-)-hydroxyhexamide, plays an important role in the in vivo serum protein binding of (-)-hydroxyhexamide.
采用超滤法检测醋磺己脲的主要代谢产物（-）-羟基己酰胺在体内和体外与兔血清的结合情况。（-）-羟基己酰胺的体内血清蛋白结合率远低于体外血清蛋白结合率。加入醋磺己脲后，（-）-羟基己酰胺的体外血清蛋白结合率被显著取代。此外，在醋磺己脲给药1.0小时后，当醋磺己脲和（-）-羟基己酰胺的浓度与体内发现的浓度相同时，（-）-羟基己酰胺的体外血清蛋白结合率与（-）-羟基己酰胺的体内血清蛋白结合率大致相似。这些结果使我们得出结论，（-）-羟基己酰胺的母体药物醋磺己脲在（-）-羟基己酰胺的体内血清蛋白结合中起重要作用。
