ESPN 50th Annual Meeting

ESPN 2017


 
Pharmacokinetics of enoxaparin in pediatric renal transplantation
DAMAMME ALICE 1 URIEN SAIK 2 SALOMON RéMI 1 LASNE DOMINIQUE 1 KRUG PAULINE 1 CHARBIT MARINA 1 TRELUYER JEAN-MARC 2 BOYER OLIVIA 1

1- HôPITAL NECKER - ENFANTS MALADES, INSTITUT IMAGINE, MARHEA, UNIVERSITé PARIS-DESCARTES, PARIS, FRANCE
2- UNITé DE RECHERCHE CLINIQUE NECKER COCHIN, AP-HP, CIC-1419 INSERM, UNIVERSITé PARIS-DESCARTES, PARIS, FRANCE.
 
Introduction:

Renal allograft vascular thrombosis is a devastating complication and the leading cause of graft loss in the 1st month after kidney transplantation in adults and in the first post-operative year in children. Prophylactic enoxaparin is commonly used in this context, but off-label in children. However, no consensus exists regarding the optimal dosing and dose-adjustment, and practices are highly heterogeneous among centers, and vulnerable to individual physician estimation and empirical practices.

Material and methods:

We conducted a retrospective study to describe enoxaparin population pharmacokinetics among renal transplanted children. Anti-Xa levels were measured in 32 pediatric renal transplanted recipients. A total of 444 observations were used for the analysis. 

Results:

The main results were 1) body-weight but not renal function was the sole covariate influencing clearance(s) and volume(s) of distribution, 2) less than 25% of children achieved the target anti-Xa activity two days after initiation of treatment 3) large inter- and intra-individual variabilities of anti-Xa activity were observed. Based on the final population model, a bayesian-based program has been developed in order to estimate the individual pharmacokinetic parameters thanks to individual anti-Xa activity observation(s) mainly after the 1st and 2nd injections, allowing determining the next enoxaparin dose that will quickly achieve an appropriate antiXa activity (targeting 0.3-0.5UI/mL).

Conclusions:

Ultimately, this Bayesian approach should help standardizing and rationalizing practices that remain to date largely heterogeneous.