Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy
Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy
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DOI：
10.1038/clpt.2008.73
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发表时间：
2008-09-01
影响因子：
6.7
通讯作者：
Lechat, P.
中科院分区：
文献类型：
--
作者：
Lebaudy, C.;Hulot, J. S.;Lechat, P.
依诺肝素常用于血栓栓塞并发症高风险的孕妇。我们进行了一项群体药代动力学研究，75名孕妇和38名非孕妇作为对照，以评估依诺肝素在妊娠期和产后期间的药代动力学。与非妊娠女性相比，妊娠女性在整个妊娠期间的药物清除率更高（分别为0.78 +/- 0.03 l/h vs. 0.52 +/- 0.03 l/h，P < 0.001），妊娠阶段没有影响。分布容积受妊娠阶段的影响，其特征为两步增加，最初的增加与前两个孕期妇女体重的增加平行，随后在妊娠的最后2个月额外增加41%，与体重的变化无关。使用依诺肝素药代动力学参数来模拟抗Xa时间曲线，我们观察到在整个妊娠期间维持相同剂量导致抗Xa活性的平均值和峰值逐渐降低。我们建议根据体重变化给予标准化剂量，以抵消伴随妊娠不同阶段的依诺肝素药代动力学变化。
Enoxaparin is frequently prescribed for pregnant women who are at high risk for thromboembolic complications. We conducted a population pharmacokinetics study with 75 pregnant women and 38 nonpregnant women as controls to evaluate enoxaparin pharmacokinetics during pregnancy and the postpartum period. Clearance of the drug was higher in the pregnant women throughout pregnancy when compared with nonpregnant women (0.78 +/- 0.03 l/h vs. 0.52 +/- 0.03 l/h, respectively P < 0.001) with the stage of the pregnancy having no influence. The volume of distribution was influenced by stage of the pregnancy, characterized by a two-step increase, with an initial rise paralleling the woman's increase in body weight during the first two trimesters, followed by an additional increase of 41% during the last 2 months of pregnancy, independent of changes in weight. Using enoxaparin pharmacokinetic parameters to simulate anti-Xa time profiles, we observed that the maintenance of the same doses throughout pregnancy resulted in a progressive reduction in mean and peak anti-Xa activities. We recommend the administration of doses normalized for body weight changes so as to counteract enoxaparin pharmacokinetic changes that accompany various stages of pregnancy.