Effects of amiodarone administration during pregnancy in Fischer 344 rats. 1991

D A Hill, and M J Reasor
Department of Pharmacology and Toxicology, West Virginia University Health Sciences Center, Morgantown 26506.

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.

UI MeSH Term Description Entries
D008098 Litter Size The number of offspring produced at one birth by a viviparous animal. Litter Sizes,Size, Litter,Sizes, Litter
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008431 Maternal-Fetal Exchange Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission. Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
D010920 Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES). Placentoma, Normal,Placentome,Placentas,Placentomes
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011270 Pregnancy, Animal The process of bearing developing young (EMBRYOS or FETUSES) in utero in non-human mammals, beginning from FERTILIZATION to BIRTH. Animal Pregnancies,Animal Pregnancy,Pregnancies, Animal
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D001724 Birth Weight The mass or quantity of heaviness of an individual at BIRTH. It is expressed by units of pounds or kilograms. Birthweight,Birth Weights,Birthweights,Weight, Birth,Weights, Birth
D005260 Female Females

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