Brophy Donald F, Carr Marcus E, Martin Erika J, Venitz Jürgen, Gehr Todd W B
Department of Pharmacy, Coagulation Special Studies Laboratory, Virginia Commonwealth University/Medical College of Virginia (VCU/MCV), Richmond, Virginia, USA.
J Clin Pharmacol. 2006 Aug;46(8):887-94. doi: 10.1177/0091270006289975.
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.
在健康志愿者、血液透析和腹膜透析受试者中研究了依诺肝素的药代动力学和药效学。抗Xa因子活性用于评估药代动力学，而凝血酶生成时间（TGT）用于评估药效学。所有受试者均皮下注射1mg/kg依诺肝素。各组之间抗Xa因子的最大浓度（Amax）和药时曲线下面积（AUC(0-12)）相似，但透析组的TGTmax显著更长（P = 0.001）。在整个12小时的研究期间，凝血酶生成时间仍显著延长，并且两个透析组的TGT药时曲线下面积（AUEC(0-12)）均有增加趋势（P = 0.07）。与其他组相比，接受血液透析的患者对依诺肝素更为敏感。这些结果表明，在透析患者中，可能存在抗Xa因子检测未发现的活性肝素代谢产物蓄积。因此，尽管抗Xa因子暴露相似，但这些受试者的凝血酶生成时间延长更为明显。需要进一步的大规模研究来证实这项探索性初步研究的结果。
