Population pharmacokinetic of nadroparin calcium (Fraxiparine®) in children hospitalised for open heart surgery

Abstract Administration of low molecular weight heparin following heart surgery in paediatric patients in order to prevent thromboembolic events results in a large variation in anti-Xa activities. A population study was undertaken to determine pharmacokinetic parameters after nadroparin calcium (Fraxiparine®) administration and the effects of potential covariates; this study included 154 children divided into two groups: a model group (124 patients) and a validation group (30 patients). The 432 anti-Xa activities were analysed using nonmem on the basis of a one-compartment model with three parameters: apparent clearance, apparent volume of distribution and absorption rate. The influence of body weight, age, sex and dose regimen (once or twice daily) were investigated. The best fit corresponds to the formula: apparent clearance (l/min)=0.541·weight 1.51 /(6.15 1.51 +weight 1.51 ) and apparent volume (l)=0.355·weight. The inter-individual variability (expressed in coefficient of variation) of these parameters are high, especially with regard to the apparent volume (92%), but no other available covariate was found to explain this variability.