Clinical pharmacology of aminocaproic and tranexamic acids

Abstract

In a systematic search for a substance with antifibrinolytic properties Okamoto and his group in Japan found that several mercapto-and aminocarbonic acids were active.Of these substances epsilon-aminocaproic acid (EACA) had the strongest antifibrinolytic effect.1 2 The Japanese workers described it as a plasmin inhibitor in vitro and useful in inhibiting proteolytic enzymes in vivo.They gave EACA in a dose of 10-20 g a day by mouth or intravenously to over 100 patients and observed no toxic effects.Their investigation did not include any metabolic studies.EACA has since been widely used and its mode of action and pharmacokinetics intensively studied.In a continued search for more potent antifibrinolytic components p-aminomethyl cyclohexane ,arboxylic acid (AMCHA) was found to be more potent than EACA.3This compound contains two stereoisomers.Independently Melander et al.4 and Okamoto et al.5 found that only the trans-form was antifibrinolytically active.The antifibrinolytically active form was called tranexamic acid (AMCA).It is 6-10 times stronger than EACA and is now used more widely.Its pharmacokinetics have been the subject of several studies.This paper surveys the pharmacology and toxicology of EACA and AMCA. PharmacokineticsAMINOCAPROIC ACID (EACA)