Pharmacokinetics of Enoxaparin After Renal Transplantation in Pediatric Patients

Abstract

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.

Current practice of antithrombotic prophylaxis in pediatric kidney transplantation—Results of an international survey on behalf of the European Society for Paediatric Nephrology

“…This finding is somewhat unclear as there are existing dosing recommendations and available blood parameters to monitor the effects of aP. 29,30 In addition, drug monitoring for aP was part of the management strategy in only slightly more than half of the transplant centers which is an inscrutable finding because thereby a critical evaluation of a dose-response correlation is not possible. 31 With respect to a critical evaluation of the risk-benefit balance of aP, drug monitoring making it all the more important as there are only few studies showing the efficacy of aP in preventing RGT outweighing risk of bleeding complications.…”

“…14,24,32 Moreover, it may be especially of interest for preventing harms for patients with LMWH and compromised renal function after pediatric KTx. 29 Expectedly, the most often used monitoring parameter for aP are partial thromboplastin time and anti-Xa-activity. 33 Though thrombophilia screening in children prior to pediatric…”

“…With respect to a critical evaluation of the risk‐benefit balance of aP, drug monitoring making it all the more important as there are only few studies showing the efficacy of aP in preventing RGT outweighing risk of bleeding complications 14,24,32 . Moreover, it may be especially of interest for preventing harms for patients with LMWH and compromised renal function after pediatric KTx 29 . Expectedly, the most often used monitoring parameter for aP are partial thromboplastin time and anti‐Xa‐activity 33…”

“…Interestingly, the information about dosing of the single drugs for aP was not only very limited due to an insufficient response rate but also highly heterogeneous which precludes a conclusive analysis. This finding is somewhat unclear as there are existing dosing recommendations and available blood parameters to monitor the effects of aP 29,30 . In addition, drug monitoring for aP was part of the management strategy in only slightly more than half of the transplant centers which is an inscrutable finding because thereby a critical evaluation of a dose‐response correlation is not possible 31 .…”

Efficacy and tolerance of selective and non-selective factor Xa inhibitors in the prevention of thrombosis in kidney disease in patients with systemic lupus erythematosus and antiphospholipid syndrome

“…Результаты фармакокинетических испытаний свидетельствуют об ассоциации между КК и показателем аХа. За небольшим исключением [17,18], большинство авторов выявили корреляцию между снижением СКФ и нарастанием аХа [9]. В нашем исследовании также наблюдалась зависимость уровня аХа от КК у больных АФСн.…”