title: Population pharmacokinetics of ϵ-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery.
abstract: BACKGROUND
  Despite demonstrated efficacy of ϵ-aminocaproic acid (EACA) in reducing blood loss in adolescents undergoing spinal fusion, there are no population-specific pharmacokinetic data to guide dosing. The aim of this study was to determine the pharmacokinetics of EACA in adolescents undergoing spinal fusion surgery and make dosing recommendations.
  
  
  METHODS
  Twenty children ages 12-17 years were enrolled, with 10 children in each of two groups based on diagnosis (idiopathic scoliosis or non-idiopathic scoliosis). Previously reported data from infants undergoing craniofacial surgery were included in the model to enable dosing recommendations over a wide range of weights, ages, and diagnoses. A population non-linear mixed effects modelling approach was used to characterize EACA pharmacokinetics.
  
  
  RESULTS
  Population pharmacokinetic parameters were estimated using a two-compartment disposition model with allometrically scaled weight and an age effect on clearance. Pharmacokinetic parameters for the typical patient were a plasma clearance of 153 ml min(-1) 70 kg(-1) (6.32 ml min(-1) kg(-0.75)), intercompartmental clearance of 200 ml min(-1) 70 kg(-1) (8.26 ml min(-1) kg(-0.75)), central volume of distribution of 8.78 litre 70 kg(-1) (0.13 litre kg(-1)), and peripheral volume of distribution of 15.8 litre 70 kg(-1) (0.23 litre kg(-1)). Scoliosis aetiology did not have a clinically significant effect on drug pharmacokinetics.
  
  
  CONCLUSIONS
  The following dosing schemes are recommended according to patient weight: weight <25 kg, 100 mg kg(-1) loading dose and 40 mg kg(-1) h(-1) infusion; weight ≤25 kg-<50 kg, 100 mg kg(-1) loading dose and 35 mg kg(-1) h(-1) infusion; and weight ≥50 kg, 100 mg kg(-1) loading dose and 30 mg kg(-1) h(-1) infusion. An efficacy trial employing this dosing strategy is warranted.
  
  
  BACKGROUND
  NCT01408823.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA strickerp@email.chop.edu.
authors.forename: P A
authors.initials: PA
authors.lastname: Stricker
authors.affiliation: Metrum Institute, Tariffville, CT, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Gastonguay
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Singh
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Fiadjoe
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Sussman
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Pruitt
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Goebel
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Department of Pediatrics, Division of Clinical Pharmacology and Therapeutics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: A F
authors.initials: AF
authors.lastname: Zuppa
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015119:Aminocaproic Acid / Q000493:pharmacokinetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D013123:Spinal Fusion
chemical_list: D015119:Aminocaproic Acid
keywords: antifibrinolytic agents; paediatrics; pharmacology; scoliosis; spinal fusion