A Comparison of the PK/PD of Tinzaparin in Pregnant Women and in Non-Pregnant Healthy Volunteers

Abstract number: P1619

Smith¹ MP, Nielsen² J, Stinson³ JC, Elleman-Olesen² M

¹¹Canterbury Health Laboratories, PO Box 151, Christchurch, New Zealand ²²LEO Pharmaceuticals, Pharmacokinetics, Ballerup, Denmark ³³LEO Pharmaceuticals, Dublin, Ireland

Low Molecular Weight Heparins (LMWH) have become the anticoagulant of choice in pregnancy. However pregnancy is unique with substantial blood volume changes giving potential to change the volume of distribution and other pharmacokinetic (PK) parameters of the LMWH. Some authorities state that the half-life of LMWH is decreased in pregnancy^1,2, although there is very little PK data available on this subject. Furthermore as each LMWH has a different PK profile, this may not be true of all LMWH. The PK/dynamics of tinzaparin in 3 studies were compared. Measuring tinzaparin concentration in units of anti Xa activity, the elimination half-life in pregnant women² who received 175 IU/kg at 36 weeks gestation was compared to PK data from18 healthy male volunteers and to a third PK study in healthy male and female volunteers. The results (mean & standard deviation) are:

Conclusion:  This limited analysis (from different studies) demonstrates no statistical difference in the plasma half-life of tinzaparin between pregnant and non-pregnant subjects. If anything, there is a tendency towards an increased plasma half-life of tinzaparin in pregnancy.

References:

1  Bates S.M.et al., Use of Antithrombotic Agents during pregnancy. Chest 2004; 126: 627–44S.

2  Smith M.P. et al., Tinzaparin sodium for thrombosis treatment and prevention during pregnancy. Amer J. Obstetrics and Gynaecology 2004; 190: 495–501.