Pharmacokinetic studies of dalteparin (Fragmin), enoxaparin (Clexane), and danaparoid sodium (Orgaran) in stable chronic hemodialysis patients.
BACKGROUND
Low molecular weight heparins (LMWHs) and danaparoid are an alternative to unfractionated heparin (UH) for anticoagulation during hemodialysis. Few data are available concerning their duration of action and whether drug accumulation occurs with continued use. We performed a prospective randomized study of the pharmacokinetics of dalteparin and enoxaparin plus danaparoid in 21 hemodialysis patients.


METHODS
Patients were randomly assigned to administration of enoxaparin, 40 mg; dalteparin, 2,500 U; or danaparoid, 34 U/kg, for 4 weeks. Antifactor Xa levels were measured at the end of weeks 1 and 4 immediately before the injection and at prescribed intervals up to 48 hours postinjection.


RESULTS
No bleeding or thrombotic episodes occurred during the study. Mean antifactor Xa activities 4 hours postinjection were 0.2 +/- 0.035 (SEM), 0.38 +/- 0.028, and 0.54 +/- 0.051 U/mL week 1 and 0.26 +/- 0.038, 0.40 +/- 0.055, and 0.64 +/- 0.050 U/mL week 4 for dalteparin, enoxaparin, and danaparoid, respectively. Both weeks 1 and 4, antifactor Xa activity 3 hours postdose was significantly greater for danaparoid sodium compared with enoxaparin and dalteparin. There were no significant differences between antifactor Xa activity week 4 versus week 1 for enoxaparin and dalteparin; however, danaparoid sodium levels during dialysis were significantly greater after 4 weeks of treatment (P = 0.0328, 1 hour; P = 0.003, 2 hours; P = 0.0128, 3 and 4 hours).


CONCLUSIONS
Dalteparin and enoxaparin provide adequate anticoagulation for hemodialysis using single bolus injections at relatively low doses. Danaparoid sodium at the current recommended dosage resulted in greater anticoagulation than enoxaparin or dalteparin and may have an
Polkinghorne
Kevan R
KR
Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia. kevan.polkinghorne@med.monash.edu.au
McMahon
Lawrence P
LP
Becker
Gavin J
GJ
D000925:Anticoagulants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002809:Chondroitin Sulfates / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017985:Dalteparin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003871:Dermatan Sulfate / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017984:Enoxaparin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005260:Female; D006496:Heparinoids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006497:Heparan Sulfate / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000628:therapy; D008297:Male; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*
D000925:Anticoagulants; D002809:Chondroitin Sulfates; D017985:Dalteparin; D003871:Dermatan Sulfate; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006496:Heparinoids; D006497:Heparan Sulfate; C035838:danaparoid