Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery

Br J Anaesth. 2013 May;110(5):788-99. doi: 10.1093/bja/aes507. Epub 2013 Jan 25.


Background: Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months undergoing craniofacial reconstruction surgery.

Methods: Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose-continuous i.v. infusion (CIVI) regimens: 25 mg kg(-1), 10 mg kg(-1) h(-1); 50 mg kg(-1), 20 mg kg(-1) h(-1); 100 mg kg(-1), 40 mg kg(-1) h(-1). Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs.

Results: Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min(-1) (3.6 ml kg(-1) min(-1)), inter-compartmental clearance of 42.4 ml min(-1) (4.8 ml min(-1) kg(-1)), central volume of distribution of 1.27 litre (0.14 litre kg(-1)), and peripheral volume of distribution of 2.53 litre (0.29 litre kg(-1)). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively.

Conclusions: EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg(-1) followed by a CIVI of 40 mg kg(-1) h(-1) is appropriate to maintain target plasma EACA concentrations in children aged 6-24 months undergoing these procedures.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aminocaproic Acid / administration & dosage
  • Aminocaproic Acid / blood*
  • Antifibrinolytic Agents / administration & dosage
  • Antifibrinolytic Agents / blood*
  • Blood Loss, Surgical
  • Blood Transfusion / methods
  • Body Weight / physiology
  • Craniofacial Abnormalities / surgery*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluid Therapy / methods
  • Humans
  • Infant
  • Male
  • Metabolic Clearance Rate / physiology
  • Models, Biological


  • Antifibrinolytic Agents
  • Aminocaproic Acid