title: Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study.
abstract: BACKGROUND
  Enoxaparin has been extensively studied in adults on its safety and efficacy during prevention of symptomatic thromboembolism when acute anticoagulation or secondary prevention is required as a result of venous thrombosis or stroke. In children, it is still used off-label and little is known about the pharmacokinetics in children.
  
  
  OBJECTIVE
  The aim of the present study was to evaluate whether a once- or twice-daily dosing regimen would be feasible in children to achieve appropriate plasma levels of enoxaparin.
  
  
  METHODS
  A population pharmacokinetic model was developed using anti-factor (F)Xa activity data from 126 children (median age: 5.9 years) receiving enoxaparin either as a once- or twice-daily dosing regimen.
  
  
  RESULTS
  A two-compartment model was adequate for describing the enoxaparin kinetics. Body weight proved to be the most predictive covariate for clearance and central volume of distribution: clearance 15 mL h⁻¹ kg⁻¹, central volume of distribution 169 mL kg⁻¹, intercompartmental clearance 58 mL h⁻¹, peripheral volume of distribution 10 L and absorption rate 0.414 h⁻¹. Interindividual variability was found to be 54% for clearance and 42% for volume of distribution.
  
  
  CONCLUSIONS
  The model is capable of describing all age groups and dosing levels of our population and predicts 12 h and 24 h enoxaparin activities sufficiently. According to our results, a once-daily enoxaparin dosing regimen with frequent monitoring is feasible. In 53.2% of the patients the median 24 h trough level was above the desired range of 0.1 IU mL⁻¹ anti-FXa activity for prophylaxis therapy.
authors.affiliation: Department of Pharmaceutical and Medical Chemistry - Clinical Pharmacy, University of Münster, Münster, Germany. tramemirjam@uni-muenster.de
authors.forename: M N
authors.initials: MN
authors.lastname: Trame
authors.forename: L
authors.initials: L
authors.lastname: Mitchell
authors.forename: A
authors.initials: A
authors.lastname: Krümpel
authors.forename: C
authors.initials: C
authors.lastname: Male
authors.forename: G
authors.initials: G
authors.lastname: Hempel
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000293:Adolescent; D000925:Anticoagulants / Q000493:pharmacokinetics; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D017984:Enoxaparin / Q000493:pharmacokinetics*; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D013923:Thromboembolism / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors