Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects

Marilynn C. Frederiksen; Dennis J. Bowsher; Tsuen Ih Ruo; Thomas K. Henthorn; Chung Hsin Ts'ao; David Green; Arthur J. Atkinson

doi:10.1038/clpt.1984.48

Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects

Marilynn C. Frederiksen, Dennis J. Bowsher, Tsuen Ih Ruo, Thomas K. Henthorn, Chung Hsin Ts'ao, David Green, Arthur J. Atkinson^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

The kinetics of ε{lunate}-aminocaproic acid (EACH) 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 t sol1 2 was 294 min and the elimination clearance was 0.19 1/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 (IC₅₀) of 63 ± 19.7 μg/ml. This agrees with the value of 0.55mM 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.

Original language	English (US)
Pages (from-to)	387-393
Number of pages	7
Journal	Clinical pharmacology and therapeutics
Volume	35
Issue number	3
DOIs	https://doi.org/10.1038/clpt.1984.48
State	Published - Mar 1984

ASJC Scopus subject areas

Pharmacology (medical)
Pharmacology

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@article{38a0013ec59c44ef96fe799e4922fc91,

title = "Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects",

abstract = "The kinetics of ε{lunate}-aminocaproic acid (EACH) 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 t sol1 2 was 294 min and the elimination clearance was 0.19 1/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 μg/ml. This agrees with the value of 0.55mM 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.",

author = "Frederiksen, {Marilynn C.} and Bowsher, {Dennis J.} and Ruo, {Tsuen Ih} and Henthorn, {Thomas K.} and Ts'ao, {Chung Hsin} and David Green and Atkinson, {Arthur J.}",

year = "1984",

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doi = "10.1038/clpt.1984.48",

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volume = "35",

pages = "387--393",

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AU - Frederiksen, Marilynn C.

AU - Bowsher, Dennis J.

AU - Ruo, Tsuen Ih

AU - Henthorn, Thomas K.

AU - Ts'ao, Chung Hsin

AU - Green, David

AU - Atkinson, Arthur J.

PY - 1984/3

Y1 - 1984/3

N2 - The kinetics of ε{lunate}-aminocaproic acid (EACH) 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 t sol1 2 was 294 min and the elimination clearance was 0.19 1/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 μg/ml. This agrees with the value of 0.55mM 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.

AB - The kinetics of ε{lunate}-aminocaproic acid (EACH) 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 t sol1 2 was 294 min and the elimination clearance was 0.19 1/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 μg/ml. This agrees with the value of 0.55mM 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.

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Kinetics of epsilon-aminocaproic acid distribution, elimination, and antifibrinolytic effects in normal subjects

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