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 sub...

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Bibliographic Details
Published inJournal of clinical pharmacology Vol. 46; no. 8; p. 887
Main Authors Brophy, Donald F, Carr, Jr, Marcus E, Martin, Erika J, Venitz, Jürgen, Gehr, Todd W B
Format Journal Article
LanguageEnglish
Published England 01.08.2006
Subjects
Adult
Anticoagulants - pharmacokinetics
Anticoagulants - pharmacology
Anticoagulants - therapeutic use
Blood Coagulation - drug effects
Drug Monitoring
Enoxaparin - pharmacokinetics
Enoxaparin - pharmacology
Enoxaparin - therapeutic use
Factor Xa Inhibitors
Female
Humans
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - therapy
Linear Models
Male
Middle Aged
Peritoneal Dialysis
Pilot Projects
Prospective Studies
Reference Values
Renal Dialysis
Thrombin Time
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Summary: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.
ISSN:0091-2700
DOI:10.1177/0091270006289975