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Kinetics of epsilon‐aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects
Author(s) -
Frederiksen Marilynn C,
Bowsher Dennis J,
Ruo Tsuen Ih,
Henthorn Thomas K,
Ts'ao ChungHsin,
Green David,
Atkinson Arthur J
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.48
Subject(s) - antifibrinolytic , chemistry , fibrinolysis , volume of distribution , aminocaproic acid , distribution (mathematics) , elimination rate constant , endocrinology , medicine , pharmacokinetics , biochemistry , surgery , mathematical analysis , blood loss , mathematics , tranexamic acid
The kinetics of €‐aminocaproic acid (EACA) distribution and elimination were studied in six normal subjects after a single 10‐gm iv dose. Steady‐state distribution volume averaged 30.0 l or 0.39 l/kg. Mean elimination t½ 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 (E max ) was used to estimate a half‐maximal inhibition (IC 50 ) of 63 ±19.7 µg/ml. This agrees with the value of 0.55 mM or 72 µg/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. Clinical Pharmacology and Therapeutics (1984) 35, 387–393; doi: 10.1038/clpt.1984.48