Frederiksen M C, Bowsher D J, Ruo T I, Henthorn T K, Ts'ao C H, Green D, Atkinson A J
Clin Pharmacol Ther. 1984 Mar;35(3):387-93. doi: 10.1038/clpt.1984.48.
The kinetics of epsilon-aminocaproic acid (EACA) distribution and elimination were studied in six normal subjects after a single 10-gm iv dose. Steady-state distribution volume averaged 30.01 or 0.39 l/kg. Mean elimination t 1/2 was 294 min and the elimination clearance was 0.19 l/min. Renal excretion of unchanged EACA accounted for 68% of its elimination and renal EACA clearance averaged 115% of creatinine clearance. EACA antifibrinolytic effect kinetics were also characterized in five of the subjects by the monitoring of clot lysis times in whole blood and platelet-rich plasma. Peak antifibrinolytic effects were observed 15 to 60 min after peak EACA plasma concentrations were attained. A model of maximal fibrinolysis inhibition (Emax) was used to estimate a half-maximal inhibition (IC50) of 63 +/- 19.7 microgram/ml. This agrees with the value of 0.55 mM or 72 microgram/ml that has been reported for the dissociation constant of the EACA-plasminogen complex and is consistent with the proposed biochemical mechanism of EACA action.
在六名正常受试者静脉注射单次10克剂量的ε-氨基己酸（EACA）后，研究了其分布和消除动力学。稳态分布容积平均为30.01或0.39升/千克。平均消除半衰期为294分钟，消除清除率为0.19升/分钟。未变化的EACA经肾排泄占其消除的68%，肾EACA清除率平均为肌酐清除率的115%。在五名受试者中，还通过监测全血和富含血小板血浆中的凝块溶解时间来表征EACA的抗纤维蛋白溶解作用动力学。在达到EACA血浆浓度峰值后15至60分钟观察到抗纤维蛋白溶解作用峰值。使用最大纤维蛋白溶解抑制（Emax）模型估计半最大抑制（IC50）为63±19.7微克/毫升。这与已报道的EACA - 纤溶酶原复合物解离常数0.55毫摩尔或72微克/毫升的值一致，并且与所提出的EACA作用的生化机制相符。
