Effects of amiodarone administration during pregnancy in Fischer 344 rats

Amiodarone is a class III anti-arrhythmic compound that is iodinated, cationic and amphiphilic in nature. The clinical use of amiodarone may be associated with various side-effects, including pulmonary and hepatic toxicity. Use of this compound during pregnancy may therefore place the fetus at risk through in utero exposure. This study was designed to observe any gross developmental effects that may be caused by the administration of amiodarone to Fischer 344 rats during pregnancy, investigate the placental transfer of amiodarone and its principal metabolite, desethylamiodarone and determine the levels of amiodarone and desethylamiodarone in the maternal and newborn lung, liver and plasma. To conduct this study, 35 mg/kg of amiodarone was administered daily to pregnant rats for either the last 7 days of pregnancy, the last 14 days of pregnancy, or for the full 22 days of pregnancy. Drug treatment had no effect on the length of gestation or litter size. Maternal weight gain was decreased only when amiodarone was administered during the last 7 days of gestation. The birthweights of the offspring were decreased, however, crown to rump length was unaffected. Both amiodarone and desethylamiodarone accumulated in the offspring through placental transfer. The levels of both compounds were greater in maternal and newborn lung when compared to maternal and newborn liver, respectively. The maternal lung and liver concentrations of both compounds were significantly higher than the respective newborn concentrations. The newborn plasma concentrations of amiodarone and desethylamiodarone were significantly lower than maternal levels indicating that the placenta may not be totally permeable to the two drugs.