A pharmacokinetic study of dalteparin (Fragmin) during late pregnancy

Seventeen women with previously verified thromboembolism were included in a pharmacokinetic evaluation of dalteparin during the third trimester of pregnancy. The bioavailability of morning subcutaneous administration of dalteparin (crossover study) was also compared with that in the evening. Fifteen women injected themselves subcutaneously with 5000 IU and two with 2500 IU dalteparin once daily. An anti-FXa activity of 0.20-0.40 IU/ml 3 h after injection was obtained. The means +/- SD, when comparing morning and evening doses for 5000 IU, were: Cmax 0.21 +/- 0.05 and 0.20 +/- 0.05 IU anti-FXa/ml, AUC 0-24 h 1.97 +/- 0.46 and 1.93 +/- 0.55 IU x h/ml and tmax 3.71 +/- 0.89 and 4.32 +/- 1.60 h, respectively (NS). The two regimens were equivalent. A measurable anticoagulant effect was still observed 16 h after injection of 5000 IU dalteparin. The half-lives after a morning and an evening dose of 5000 IU dalteparin were 4.92 +/- 2.80 and 3.87 +/- 1.15 h, respectively (NS). There were no changes in thrombin marker levels during the two pharmacokinetic measurements.