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  • Title: Metabolic fate of the new cardiotonic denopamine in animals. 3rd communication: placental transfer and excretion into milk in the rat.
    Author: Naito K, Furuuchi S, Otsuka M, Harigaya S.
    Journal: Arzneimittelforschung; 1986 Apr; 36(4):656-65. PubMed ID: 3718590.
    Abstract:
    3H-labelled (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol (denopamine, TA-064) was administered orally to pregnant rats at a dose of 5 or 60 mg/kg on the 14th or 20th day of pregnancy. Irrespective of the doses and the stages of pregnancy, radioactivity in the fetus reached a peak at 30 min after administration, being 1/7 to 1/25 of the maternal plasma levels. Total radioactivity in each fetus at 30 min was estimated to be only about 0.002 to 0.06% of the dose. Disappearance of radioactivity from the fetus, uterus and amniotic fluid was slightly slower than that from the maternal plasma. After 3H-denopamine (5 mg/kg) was orally administered to lactating rats on the 12th day after delivery, radioactivity in milk was generally lower than in the blood of the dams, and time to the peak levels in milk tended to delay as compared with that in the blood. The levels of radioactivity in the blood of the sucklings, nursed by their dams, at 1 h after nursing were about 1/30 of the maternal blood levels, showing a slight transfer of the drug and/or its metabolites via milk. At 24 h after administration, radioactivity levels in the sucklings decreased to near the detection limit. The results of whole body autoradiography were generally consistent with the quantitative data on the placental transfer and excretion into milk.
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