Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects.
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.
D000328:Adult; D000614:Aminocaproates / Q000378:metabolism*; D015119:Aminocaproic Acid / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male
D000614:Aminocaproates; D015119:Aminocaproic Acid