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

• Published in: Therapeutic drug monitoring Vol. 22; no. 5; pp. 582 - 588
• Main Authors: SCHMOLLING, Jan, RENKE, Kirsten, RICHTER, Oliver, PFEIFFER, Kerstin, SCHLEBUSCH, Harald, HÖLLER, Tobias
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-10-2000
• Subjects: Amiodarone - pharmacokinetics; Amiodarone - therapeutic use; Anti-Arrhythmia Agents - pharmacokinetics; Anti-Arrhythmia Agents - therapeutic use; Antiarythmic agents; Area Under Curve; Biological and medical sciences; Cardiovascular system; Digoxin - pharmacokinetics; Digoxin - therapeutic use; Female; Fetal Diseases - drug therapy; Flecainide - pharmacokinetics; Flecainide - therapeutic use; Humans; In Vitro Techniques; Medical sciences; Pharmacology. Drug treatments; Placenta - blood supply; Placenta - metabolism; Pregnancy; Regional Blood Flow; Tachycardia, Supraventricular - drug therapy; Umbilical Veins - physiology; Venous Pressure; Human; Digoxin; Placental transfer; Amiodarone; Antiarrhythmic agent; In vitro; Iodine Organic compounds; Pressure; Placenta; Mother embryonal transfer; Glycoside; Flecainide; Pharmacokinetics; Umbilical vein; Digitalis drug
• ISSN: 0163-4356; 1536-3694
• DOI: 10.1097/00007691-200010000-00013

Clinical observations suggest that flecainide might pass the placenta more easily than digoxin, and that its transfer is less disturbed in case of hydrops fetalis than that of digoxin. The purpose of the study was to compare the materno-fetal transplacental transfer of digoxin, flecainide, and amiodarone, another antiarrhythmic agent used in the treatment of fetal tachyarrhythmia, and to assess the effect of an elevated umbilical venous pressure (UVP) on the transfer rate. Isolated lobules of 16 human placentas were dually perfused after spontaneous delivery or caesarean section. The transplacental transfer (area under the curve in the maternal compartment [maternal AUC], area under the curve in the fetal compartment [fetal AUC], kinetic parameters) 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 elevating 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 detectable in the fetal compartment. An elevation of the UVP reduced the influx of digoxin and flecainide into the fetal compartment (fetal AUC) from 11.5% +/- 2.0%/min to 7.4% +/- 1.9%/min and from 9.3% +/- 4.1% to 4.7% +/- 1.4%/min, respectively. Materno-fetal transplacental transfer of digoxin, flecainide, and amiodarone decreases in this sequence. Fetal cardiac insufficiency accompanied by an elevation of the UVP might reduce the transplacental transfer of these drugs, although no significant difference could be found between the reduction of transfer of digoxin and flecainide.