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

P A Stricker1, A F Zuppa, J E Fiadjoe

  • 1Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-4399, USA.

British Journal of Anaesthesia
|January 29, 2013
PubMed

Insights

Epsilon-aminocaproic acid (EACA) dosing in infants undergoing surgery was studied. A loading dose of 100 mg/kg followed by a continuous infusion of 40 mg/kg/h is recommended for children aged 6-24 months.

Area of Science:

  • Pharmacology
  • Pediatric Surgery
  • Drug Metabolism

Background:

  • Clinical pharmacology of epsilon-aminocaproic acid (EACA) is crucial for pediatric drug administration.
  • EACA is an antifibrinolytic agent used in surgical settings.
  • Limited pharmacokinetic data exists for EACA in infants.

Purpose of the Study:

  • To determine the pharmacokinetics (PKs) of EACA in infants aged 6-24 months.
  • To establish appropriate dosing regimens for EACA in this pediatric population.
  • To inform rational drug administration of EACA during craniofacial reconstruction surgery.

Main Methods:

  • Sequential enrollment of infants into three escalating dose regimens of EACA.
  • Continuous intravenous infusion (CIVI) of EACA was administered.
  • Plasma EACA concentrations were quantified using LC-MS/MS.
  • Population non-linear mixed-effects modeling was employed to characterize PKs.

Main Results:

  • A two-compartment disposition model with allometric weight and age effects described EACA PKs.
  • Typical patient PK parameters were estimated (clearance, volumes of distribution).
  • Intra-operative clearance and central volume of distribution were lower than pre-/postoperative values.

Conclusions:

  • EACA clearance demonstrated a positive correlation with both weight and age.
  • Weight-based dosing of EACA is supported by the observed pharmacokinetic relationships.
  • A recommended EACA regimen of 100 mg/kg loading dose followed by 40 mg/kg/h CIVI for infants aged 6-24 months.
Abstract

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