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Pharmacokinetics of Enoxaparin After Renal Transplantation in Pediatric Patients
Author(s) -
Damamme Alice,
Urien Saïk,
Borgel Delphine,
Lasne Dominique,
Krug Pauline,
Krid Saoussen,
Charbit Marina,
Salomon Rémi,
Treluyer JeanMarc,
Boyer Olivia
Publication year - 2018
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1289
Subject(s) - medicine , renal function , dosing , transplantation , pharmacokinetics , population , volume of distribution , thrombosis , intensive care medicine , surgery , environmental health
Enoxaparin is commonly used in the prevention of renal allograft vascular thrombosis but off‐label in children, and no consensus exists regarding the optimal dosing and dose adjustment. In this retrospective study, 444 anti‐Xa levels were obtained from 30 pediatric renal transplant recipients in order to investigate enoxaparin population pharmacokinetics. The main results were (1) 25% of children achieved the target anti‐Xa activity 36 hours after initiation of treatment, (2) anti‐Xa time courses were best described by a 1‐compartment open model with first‐order absorption, (3) body weight but not renal function was the sole covariate influencing clearance and volume of distribution, and (4) large between‐subject and between‐occasion variabilities in anti‐Xa activity were observed. However, creatinine‐based estimated glomerular filtration rate in the first post–renal transplantation hours may not reliably reflect the actual renal function of the children. Based on the final population model, a Bayesian‐based program was developed in order to estimate the individual pharmacokinetic parameters on a single anti‐Xa measurement, allowing determination of the next enoxaparin dose that will quickly achieve an appropriate anti‐Xa activity (targeting 0.3‐0.5 IU/mL) and anticoagulation. Finally, these results should help standardize practices that remain to date largely heterogeneous in pediatric intensive care units.