Digoxin, flecainide, and amiodarone transfer across the placenta and the effects of an elevated umbilical venous pressure on the transfer rate

Clinical observations suggest that flecainide might pass the placenta more easily than digoxin, and that its transfer is less disturbed in case of hyd rops fetalis than that of digoxin. The purpose of the study was to compare the materno-fetal transplacental transfer of digoxin, flecainide, and amiod arone, another antiarrhythmic agent used in the treatment of fetal tachyarr hythmia, and to assess the effect of an elevated umbilical Venous pressure (UVP) on the transfer rate. Isolated lobules of 16 human placentas were dua lly perfused after spontaneous delivery or caesarean section. The transplac ental transfer (area under the curve in the maternal compartment [maternal AUC], area under the curve in the fetal compartment [fetal AUC], kinetic pa rameters) of digoxin. flecainide, and amiodarone was calculated after these drugs were added to the maternal circuit, in five experiments, the effect of increased UVP on the transplacental transfer rate was assessed by elevat ing the UVP by 10 cm H2O. Flecainide efflux out of the maternal compartment was significantly greater than that of digoxin (maternal AUC 57.4% +/- 5.1 %/min vs 73.9% +/- 1.5%/min), whereas the flecainide influx into the fetal circulation was smaller (fetal AUC 9.3% +/- 4.1%/min vs 11.5% +/- 2.0%/min) . Only in 50% of the experiments were the smallest amounts of amiodarone de tectable in the fetal compartment. An elevation of the UVP reduced the infl ux of dioxin and flecainide into the fetal compartment (fetal AUG) from 11. 5% +/- 2.0%/min tp 7.4% +/- 1.9%/min and from 9.3% +/- 4.1% to 4.7% +/- 1.4 %/min, respectively. Materno-fetal transplacental transfer of digoxin, flec ainide, and amiodarone decreases in this sequence. Fetal cardiac insufficie ncy accompanied by an elevation of the WP might reduce the transplacental t ransfer of these drugs, although no significant difference could be found b etween the reduction of transfer of digoxin and flecainide.