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Metabolic Fate of NKH477. (2). Blood Concentration, Distribution, Excretion and Effects on Drug-Metabolizing Enzyme System in Rats after Repeated Intravenous Administration.

  • MATSUMOTO Shin-ichi
    Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd
  • IRIE Tsuyoshi
    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
  • SEKI Hideaki
    Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd
  • NINOMIYA Shin-ichi
    Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd
  • TAKAO Atsushi
    Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd
  • OOTUBO Miwa
    Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd
  • TAKAICHI Matsuo
    Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd
  • ESUMI Yoshio
    Tokai Research Laboratories, Daiichi Pure Chemicals Co., Ltd

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Other Title
  • 急性心不全治療薬NKH477の体内動態 (第2報)  ラットにおける反復静脈内投与後の血液中濃度,分布,排せつおよび肝薬物代謝酵素系に及ぼす影響
  • 急性心不全治療薬NKH477の体内動態(第2報):フットにおける反復静脈内投与後の血液中濃度,分布,排泄および肝薬物代謝酵素系に及ぼす影響

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Abstract

The blood concentration, distribution and excretion of radioactivity were investigated in male rats after daily intravenous administration of 14C-NKH477 for 21 days. The effects of NKH477 on hepatic drug metabolizing enzyme system were also investigated in male rats.<BR> 1. The radioactivity in the blood at 24 hr after daily administration rose as number of dose increased, the elimination of radioactivity from the blood after the last dosing was slower than that after a single dosing.<BR> 2. In most tissues, the radioactivity accumulated during the period of repeated administration, especially in the spleen, blood, kidney and mesenteric lymph node that rose markedly. Disappearance of radioactivity from most tissues after the last dosing was slower compared with that after a single dosing.<BR> 3. Within 168 hr after a repeated administration for 21 days, urinary and fecal excretion amounted to 7.8% and 88.9% of cumulative dose, respectively. The ratio of excretion between urine and feces was approximately the same as after a single dosing.<BR> 4. Repeated administration of NKH477 at doses of 0.3 and 1.0 mg/kg/day for 7 days had no effect on liver weight, microsomal cytochrome P-450 contents and hepatic drug-metabolizing enzyme system.

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