Kani Chara, Markantonis Sophia L, Nicolaou Chara, Maggina Nina
Laboratory of Biopharmaceutics and Pharmacokinetics, Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, 15771 Athens, Greece.
J Crit Care. 2006 Mar;21(1):79-84. doi: 10.1016/j.jcrc.2005.09.056.
The objective of this study was to investigate the pharmacodynamic parameters of dalteparin in patients with renal insufficiency under intensive care.
In this open, nonrandomized, nonblinded, prospective, single-dose observational study, 10 critically ill patients with renal insufficiency (mean creatinine clearance = 29.5 +/- 6.42 mL/min) were administered a single 5000-IU subcutaneous dose of dalteparin.
Dalteparin blood levels were estimated indirectly over a 12-hour period by measuring anti-Xa activity and by performing a clotting assay known as the ATHU (AHEPA Thrombosis and Hemostasis Unit) test. Maximum anti-Xa activity (ie, 0.42 +/- 0.13 IU/mL) was achieved 4 hours after administration (in 8 of 10 patients). Adequate anticoagulant activity was maintained throughout the 12-hour dosage interval in all study patients. However, at time 0 hour of the study, 36 hours after the administration of a previous dose of dalteparin, considerable anti-Xa activity (ie, 0.39 +/- 0.11 IU/mL) was measured in 6 patients. A good correlation was found between anti-Xa activity and the results of the ATHU test.
The presence of medium/severe edema and the concurrent administration of 1 to 3 inotropic drugs appear to contribute to a decrease in the rate of elimination of dalteparin, resulting in a greater-than-expected (as a result of decreased renal function) prolongation of its pharmacologic activity. We recommend that care be taken with repeated dosing of dalteparin in intensive care unit patients taking inotropic drugs until observed results can be confirmed.
本研究的目的是调查在重症监护下肾功能不全患者中达肝素的药效学参数。
在这项开放、非随机、非盲、前瞻性、单剂量观察性研究中,对10例肾功能不全的重症患者(平均肌酐清除率 = 29.5 +/- 6.42 mL/分钟)皮下注射单剂量5000 IU的达肝素。
通过测量抗Xa活性并进行一种称为ATHU(AHEPA血栓形成和止血单位)试验的凝血测定,在12小时内间接估计达肝素的血药浓度。给药后4小时达到最大抗Xa活性(即0.42 +/- 0.13 IU/mL)(10例患者中的8例)。所有研究患者在整个12小时给药间隔内均维持了足够的抗凝活性。然而,在研究的0小时,即前一剂达肝素给药后36小时,6例患者测得相当高的抗Xa活性(即0.39 +/- 0.11 IU/mL)。抗Xa活性与ATHU试验结果之间发现有良好的相关性。
中度/重度水肿的存在以及同时使用1至3种血管活性药物似乎导致达肝素消除率降低,导致其药理活性延长幅度大于预期(由于肾功能下降)。我们建议,在重症监护病房中使用血管活性药物的患者重复使用达肝素时应谨慎,直到观察结果得到证实。