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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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liboygg: ½ð±Ò+100, ·­ÒëEPI+1, ¡ï¡ï¡ï¡ï¡ï×î¼Ñ´ð°¸, лл£¬ÌõÀíºÜÇåÎú 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.
ÒòΪÁÙ´²ÊÔÑéÉв»ÄÜÖ±½Ó²âÁ¿µÍ·Ö×Ó¸ÎËØµÄˮƽ¡£ Ò©Îï´úл¶¯Á¦Ñ§ÁìÓòÔø¾­ÓÐÑо¿Ê¹ÓÃÕâÖÖ»îÐÔÌæ´úÎïÀ´´úÌæ¿¹XaÒò×Ó»îÐÔ¡£È»¶ø´Ë·½·¨ÈδæÔÚһЩÀ§ÄÑ¡£Ê×ÏÈ¿¹XaÒò×Ó»îÐÔ·´Ó³µÄÊǸÎËØµÄ´æÔÚÁ¿¶ø²»ÊÇ¿¹ÑªË¨×÷Óõij̶ȡ£Æä´ÎÔÚͬµÈµÄ¿¹Xa»îÐÔ×÷ÓÃÏ£¬²»Í¬µÄ²úÆ·IIa¿¹ÌåÒòËØµÄ»îÐÔÓÐÃ÷ÏԵIJîÒì¡£×îºó¿¹XaÒò×ÓˮƽԤ²âÊÇ·ñ»áµ¼Ö³öѪ²¢·¢Ö¢ÁÙ´²ÉÏ»¹´æÔÚÕùÒé¡£
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.
һЩÑо¿Õß¶ÔCKD´¦ÓÚ1-3ÆÚµÄ»¼ÕßÔÚ²»Í¬µÄµÍ·Ö×ÓÁ¿¸ÎËØµÄÌõ¼þϵÄÒ©´ú¶¯Á¦Ñ§ºÍ¶¯Ì¬½øÐÐÁËÑо¿¡£ÔËÓÃTIMI IIAÊÔÑ飬ʹÓð¢Ë¾Æ¥ÁÖ¼ÓÒÀŵ¸ÎËØ£¬¶Ô»¼Õß¾­ÒÀŵ¸ÎËØÖÎÁƺóµÄÒ©´ú¶¯Á¦ºÍҩЧÊý¾Ý½øÐÐÁËÆÀ¹À¡£sCr ˮƽÔÚ2.0 mg/dL »òÕß´óÓÚ[ 177  mol/L]µÄ»¼ÕßÅųýÔÚ´ËʵÑéÖ®Íâ.
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]).
CrClÊÇÒÁŵ¸ÎËØÇå³ýÐÔ£¬ÇúÏßÏÂÃæ»ýºÍ¿¹Xa»îÐÔÈýÕß×î´óµÄÓ°ÏìÒòËØ¡£Ó뻼ÕßCrClÔÚ¸ßÓÚ88 mL/min [1.47 mL/s]µÄÇé¿öÏÂÏà±È£¬ CrClÉÙÓÚ40 mL/min (0.67mL/s)µÄ»¼ÕßÒ©ÎïµÄÇå³ýÂÊϽµÁË22%¡£
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.
Ñо¿Õ߸ù¾ÝÏû³ýÇúÏߣ¨¼ûͼ2£©µÄÏßÐÔÌØÕ÷ÍÆ¶Ïµ±»¼ÕßCrClÉÙÓÚ20 mL/min (0.33mL/s)ʱÒÀŵ¸ÎËØµÄÇå³ýÂÊ¿ÉÒÔϽµ´óÔ¼50%¡£ÓëÉö¹¦ÄÜÕý³£Õߣ¨P = 0.0017£¬P = 0.0044£¬·Ö±ð£©Ïà±È£¬ËäÈ»ÕâÖÖÇé¿öºÜÉÙ£¬ CrClСÓÚ40 mL/min (0.67 mL/s) »¼ÕßÓиü´óµÄ²¨¹ÈºÍ¸ß¿¹Xa»îÐÔ²¢ÇÒ°éÓдó³öѪµÄ¿ÉÄÜÐԱȽϴó¡£
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