The pharmacokinetics of enoxaparin do not correlate with its pharmacodynamic effect in patients receiving dialysis therapies.
The pharmacokinetics and pharmacodynamics of enoxaparin were studied in healthy volunteers and hemodialysis and peritoneal dialysis subjects. Antifactor Xa activity estimated the pharmacokinetics, whereas thrombin generation time (TGT) estimated the pharmacodynamics. Enoxaparin 1 mg/kg was given subcutaneously to all subjects. Antifactor Xa Amax and AUC(0-12) were similar between groups, but the TGTmax was significantly greater in the dialysis groups (P = .001). The thrombin generation time remained significantly more prolonged throughout the 12-hour study period, and there was a trend toward greater TGT AUEC(0-12) for both dialysis groups (P = .07). Patients receiving hemodialysis had greater sensitivity to enoxaparin compared to the other groups. These results suggest that in dialysis patients, there may be accumulation of active heparin metabolites that are undetected by the antifactor Xa assay. Therefore, these subjects exhibit greater thrombin generation time prolongation despite similar antifactor Xa exposure. Further large-scale studies are needed to corroborate the results of this exploratory pilot study.
Brophy
Donald F
DF
Department of Pharmacy, Coagulation Special Studies Laboratory, Virginia Commonwealth University/Medical College of Virginia (VCU/MCV), Richmond, Virginia, USA.
Carr
Marcus E
ME
Martin
Erika J
EJ
Venitz
Jürgen
J
Gehr
Todd W B
TW
D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D016903:Drug Monitoring; D017984:Enoxaparin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010865:Pilot Projects; D011446:Prospective Studies; D012016:Reference Values; D006435:Renal Dialysis; D013918:Thrombin Time
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors