[Transplacental passage of doxorubicin]

The transplacental passage of doxorubicin, an anthracycline used for lymphoproliferative disorders and breast cancer, was studied by in vitro perfusion of term human placenta. Placentas from women with uncomplicated pregnancy were collected immediately after vaginal delivery and put into a 37 degree C thermostatically-controlled hood. A cotyledon was chosen and placed into the perfusion chamber; fetal and maternal compartments of the isolated lobe were thus perfused with separated "open" circuits. Perfusion of fetal surface of the placenta was started immediately at a flow rate of 6 ml/mn and then so was the perfusion of the intervillous space at a rate of 12 ml/mn. Perfusion medium used was Earle's solution. Antipyrine, to validate experience, and doxorubicin were added to the maternal perfusate. Samples were collected from arterial inflow and venous outflow respective of the maternal and fetal compartment and timed measurements of the fetal venous return were used to calculate flow rates. After a stability study of doxorubicin solutions under experimental conditions, the transplacental transfer of doxorubicin was then investigated for three doses: 3 mg/l, 30 mg/l and 150 mg/l. The global transfer value is low (2.96% +/- 0.75%) and doesn't seem dose-dependent. Adriamycinol, a plasma doxorubicin metabolite, has not been found even for the greatest concentration. The low transfer value can explain the rarity of fetal accidents in clinical reports.