Report: Dabigatran moves from mother to fetus

New research published in Obstetrics & Gynecology indicates the oral thrombin inhibitor, dabigatran, and its prodrug, dabigatran etexilate mesylate transfer from pregnant women to their fetuses via the placenta and could potentially affect fetal blood coagulation.

“From a clinical perspective, these data suggest that, pending further study, dabigatran should not be used for anticoagulation of pregnant women, because the drug may have an adverse effect on fetal blood coagulation," researchers wrote in the report.

Canadian researcher Priya Bapat, BMSc, Departments of Pharmacology and Toxicology and Pediatrics, University of Toronto, Ontario, Canada, and colleagues used 6 placentas from healthy term pregnancies after cesarean delivery to conduct perfusion experiments.

The researchers examined the transplacental transfer of dabigatran and dabigatran etexilate mesylate separately using the ex vivo dual perfusion of an isolated human placental cotyledon.

At a concentration of 35 ng/mL, dabigatran was added to maternal circulation at the start of the experimental phase. Both maternal and fetal samples were taken one hour after administration and three hours later.

Placenta perfusions were also conducted using dabigatran etexilate mesylate (at an initial maternal concentration of 3.5 ng/mL).

Researchers found that, after introducing 35 ng/mL of dabigatran, the rate of disappearance from the maternal circulation was faster during the first 30 minutes than the remainder of the perfusion. After three hours, the median fetal concentration of dabigatran was 4.96 ng/mL, and the median fetal-to-maternal ratio was 0.33.

With the 3.5 ng/mL dabigatran etexilate mesylate, there was a median fetal concentration of 0.19 ng/mL after the three-hour perfusion.

“The results of this perfusion study demonstrate that dabigatran crosses the term human placenta to some extent. Future studies will need to explore the role of placental drug transporters, especially P-glycoprotein, in affecting this process,” the researchers concluded.