Metabolic Fate of NKH477. (3). Feto-Placental Transfer and Excretion into Milk in Rats after a Single Intravenous Administration.

  • IRIE Tsuyoshi
    Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd
  • MATSUMOTO Shin-ichi
    Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd
  • GODA Rika
    Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd
  • EKI Toshiko
    Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd
  • YAMASHITA Kouwa
    Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd

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  • 急性心不全治療薬NKH477の体内動態 (第3報)  ラットにおける単回静脈内投与時の胎盤通過性および乳汁移行性

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Abstract

Feto-placental transfer and excretion into milk of 14C-NKH477 were investigated in pregnant and lactating rats after a single intravenous administration.<BR> 1. From the results of whole body autoradiography in pregnant rats performed on the 17th of gestation, the levels of radioactivities in placenta and amnion were similar as that in the maternal blood within 6 hours after a single intravenous administration of 14C-NKH477, and the radioactivities in these tissues decreased to tracer levels at 24 hours after administration. There were no radioactivities present in fetus and amniotic fluid to 24 hours after administration.<BR> 2. The radioactivity levels in amniotic fluid, fetus and fetal liver were lower than those of amnion and placenta after a single intravenous administration of 14C-NKH477 to rats on the 14th or 18th day of pregnancy. The levels of radioactivity in fetus at 5 min and 1 hour after administration were 1/3 ?? 1/9 of the concentrations in maternal blood. The amounts of the radioactivity transferred to fetus were low both on the 14th and 18th day of pregnancy, and the radioactivity slightly distributed in fetus was eliminated rapidly.<BR> 3. After a single intravenous administration of 14C-NKH477 to lactating rats on the 11th day after delivery, the radioactivity was detected in the milk, and the ratio of milk to plasma within 24 hours after administration was 1.0 ?? 2.2.

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