Hicks D R, Kraml M, Cayen M N, Dubuc J, Ryder S, Dvornik D
Clin Pharmacol Ther. 1984 Oct;36(4):493-9. doi: 10.1038/clpt.1984.209.
The kinetics of tolrestat, a potent inhibitor of aldose reductase, were examined. Serum concentrations of tolrestat and of total 14C were measured after dosing normal subjects and subjects with diabetes with 14C-labeled tolrestat. In normal subjects, tolrestat was rapidly absorbed and disappearance from serum was biphasic. Distribution and elimination t 1/2s were approximately 2 and 10 to 12 hr, respectively, after single and multiple doses. Unchanged tolrestat accounted for the major portion of 14C in serum. Radioactivity was rapidly and completely excreted in urine and feces in an approximate ratio of 2:1. Findings were much the same in subjects with diabetes. In normal subjects, the kinetics of oral tolrestat were independent of dose in the 10 to 800 mg range. Repetitive dosing did not result in unexpected cumulation. Tolrestat was more than 99% bound to serum protein; it did not compete with warfarin for binding sites but was displaced to some extent by high concentrations of tolbutamide or salicylate.
对醛糖还原酶的强效抑制剂托瑞司他的动力学进行了研究。给正常受试者和糖尿病受试者服用14C标记的托瑞司他后，测定了托瑞司他和总14C的血清浓度。在正常受试者中，托瑞司他吸收迅速，血清中的消除呈双相性。单次和多次给药后，分布半衰期和消除半衰期分别约为2小时和10至12小时。血清中14C的主要部分为未改变的托瑞司他。放射性迅速且完全地经尿液和粪便排出，比例约为2:1。糖尿病受试者的结果大致相同。在正常受试者中，口服托瑞司他的动力学在10至800毫克范围内与剂量无关。重复给药未导致意外蓄积。托瑞司他与血清蛋白的结合率超过99%；它不与华法林竞争结合位点，但在高浓度甲苯磺丁脲或水杨酸盐的作用下会被部分置换。
