Premium
Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study
Author(s) -
TRAME M. N.,
MITCHELL L.,
KRÜMPEL A.,
MALE C.,
HEMPEL G.,
NOWAKGÖTTL U.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2010.03964.x
Subject(s) - medicine , dosing , volume of distribution , regimen , pharmacokinetics , population , venous thrombosis , thrombosis , anesthesia , environmental health
Summary. 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. Objectives: 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. Patients/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. Conclusion: 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.