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liboygg

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Because in clinical practice, it is not possible to measure LMWH levels directly; pharmacokinetic studies have used such surrogate markers of activity as anti-Xa activity, but there are a number of difficulties with this. First, anti-Xa activity represents the amount of heparin present, rather than the degree of antithrombotic effect. Second, at equivalent anti-Xa activities, antifactor IIa activity of different products shows marked variations. Finally, conflicting evidence exists about whether anti-Xa levels predict for bleedingcomplications clinically.
Several studies have looked at the pharmacokinetics and dynamics of different LMWHs in patients with CKD stages 1 to 3. In patients enrolled in the TIMI IIA trial, (aspirin plus enoxaparin), pharmacokinetic and pharmacodynamic profiles after enoxaparin therapy were assessed. Patients with an sCr level of 2.0 mg/dL or greater
[177 mol/L] were excluded from the trial. CrCl was the most influential factor on enoxaparin clearance, area under the curve, and anti-Xa activity. Drug clearance was decreased by 22% in patients with a CrCl less than 40 mL/min (0.67mL/s) compared with those with greater CrCls (mean, 88 mL/min [1.47 mL/s]). The linear character of the elimination curve (Fig 2) led the investigators to extrapolate that enoxaparin clearance would be reduced by approximately 50% in patients with a CrCl less than 20 mL/min (0.33mL/s). Although numbers were small, patients
with a CrCl less than 40 mL/min (0.67 mL/s) had greater trough and peak anti-Xa activity compared with those with normal renal function (P=0.0017 and P =0.0044, respectively) and were more likely to experience major hemorrhagic events.
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李氏氏

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liboygg: 金币+100, 翻译EPI+1, ★★★★★最佳答案, 谢谢,条理很清晰 2013-01-04 17:03:08
Because in clinical practice, it is not possible to measure LMWH levels directly; pharmacokinetic studies have used such surrogate markers of activity as anti-Xa activity, but there are a number of difficulties with this. First, anti-Xa activity represents the amount of heparin present, rather than the degree of antithrombotic effect. Second, at equivalent anti-Xa activities, antifactor IIa activity of different products shows marked variations. Finally, conflicting evidence exists about whether anti-Xa levels predict for bleeding complications clinically.
因为临床试验尚不能直接测量低分子肝素的水平。 药物代谢动力学领域曾经有研究使用这种活性替代物来代替抗Xa因子活性。然而此方法任存在一些困难。首先抗Xa因子活性反映的是肝素的存在量而不是抗血栓作用的程度。其次在同等的抗Xa活性作用下,不同的产品IIa抗体因素的活性有明显的差异。最后抗Xa因子水平预测是否会导致出血并发症临床上还存在争议。
Several studies have looked at the pharmacokinetics and dynamics of different LMWHs in patients with CKD stages 1 to 3. In patients enrolled in the TIMI IIA trial, (aspirin plus enoxaparin), pharmacokinetic and pharmaco dynamic profiles after enoxaparin therapy were assessed. Patients with an sCr level of 2.0 mg/dL or greater [ 177  mol/L] were excluded from the trial.
一些研究者对CKD处于1-3期的患者在不同的低分子量肝素的条件下的药代动力学和动态进行了研究。运用TIMI IIA试验,使用阿司匹林加依诺肝素,对患者经依诺肝素治疗后的药代动力和药效数据进行了评估。sCr 水平在2.0 mg/dL 或者大于[ 177  mol/L]的患者排除在此实验之外.
CrCl was the most influential factor on enoxaparin clearance, area under the curve, and anti-Xa activity. Drug clearance was decreased by 22% in patients with a CrCl less than 40 mL/min (0.67mL/s) compared with those with greater CrCls (mean, 88 mL/min [1.47 mL/s]).
CrCl是伊诺肝素清除性,曲线下面积和抗Xa活性三者最大的影响因素。与患者CrCl在高于88 mL/min [1.47 mL/s]的情况下相比, CrCl少于40 mL/min (0.67mL/s)的患者药物的清除率下降了22%。
The linear character of the elimination curve (Fig 2) led the investigators to extrapolate that enoxaparin clearance would be reduced by approximately 50% in patients with a CrCl less than 20 mL/min (0.33mL/s). Although numbers were small, patients with a CrCl less than 40 mL/min (0.67 mL/s) had greater trough and peak anti-Xa activity compared with those with normal renal function (P =0.0017 and P =0.0044, respectively) and were more likely to experience major hemorrhagic events.
研究者根据消除曲线(见图2)的线性特征推断当患者CrCl少于20 mL/min (0.33mL/s)时依诺肝素的清除率可以下降大约50%。与肾功能正常者(P = 0.0017,P = 0.0044,分别)相比,虽然这种情况很少, CrCl小于40 mL/min (0.67 mL/s) 患者有更大的波谷和高抗Xa活性并且伴有大出血的可能性比较大。
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