Changes in enoxaparin pharmacokinetics during pregnancy and implications for antithrombotic therapeutic strategy.

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.