Nephrol Dial Transplant (2003) 18: 2348-2353
© 2003 European Renal Association-European Dialysis and Transplant Association
Original Article
Pharmacokinetics of the low molecular weight heparin enoxaparin during 48 h after bolus administration as an anticoagulant in haemodialysis
1Service de Néphrologie, Hôpital de la Conception, Marseille, 2Laboratoire de Pharmacologie Médicale et Clinique, UFR de Médecine, Marseille and 3Laboratoire Central, Hôpital Sainte-Marguerite, Marseille, France
Correspondence and offprint requests to: Philippe Brunet, Service de Néphrologie, Hôpital de la Conception, 147 Boulevard Baille, F-13385 Marseille Cedex 05, France. Email: pbrunet{at}ap-hm.fr
Background. The interest of low molecular weight heparins (LMWH) regarding bleeding risk is controversial in renal failure patients. In haemodialysis patients, there are very few data on the pharmacokinetics of LMWH after the end of the session. The aim of the study was to evaluate the duration of anticoagulation after bolus administration of the LMWH enoxaparin at the start of haemodialysis.
Methods. The pharmacokinetics of enoxaparin were studied during the 48 h following a single bolus injection at the start of the dialysis session in 30 chronic haemodialysis patients. Pharmacokinetics were determined using a population approach (Non Linear Mixed Effects Modelling).
Results. A single injection of enoxaparin at 60 U IU/kg (4000 ± 455 IU) led to an anti-Xa activity higher than 1.2 IU/ml during the first 2 h of the session, and between 0.4 and 1.2 IU during the third and fourth hours. After the end of the session, anti-Xa activity remained higher than 0.4 IU/ml up to 10 h after injection, and higher than 0.1 IU/ml up to 24 h. The pharmacokinetic model showed that only weight improved the predicted vs observed anti-Xa activity plot. The model was used to simulate single and multiple dosing with decreased enoxaparin doses. Whatever the procedure, anti-Xa activity remained high (>0.22 ± 0.99 UI/ml) up to 12 h after the start of the dialysis session.
Conclusions. These results suggest that haemodialysis patients receiving the LMWH enoxaparin during dialysis are at risk of bleeding up to 10 h after the injection.
Keywords: anticoagulation; anti-Xa; enoxaparin; haemodialysis; nonmem; population pharmacokinetics
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