Studies on the Metabolic Fate of M17055, a Novel Diuretic. (3): Plasma Concentration, Distribution and Excretion of Radioactivity in Male Rats after Repeated Daily Intravenous Administration of [14C]M17055.

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  • NAKAJIMA Hiroyuki
    Drug Metabolism and Pharmakokinetics Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
  • NAKANISHI Takeshi
    Drug Metabolism and Pharmakokinetics Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
  • NABA Hiroyasu
    Drug Metabolism and Pharmakokinetics Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
  • IDA Keiichi
    Drug Metabolism and Pharmakokinetics Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.
  • OHZAWA Nobuo
    Drug Metabolism and Pharmakokinetics Laboratory, Research Center, Mochida Pharmaceutical Co., Ltd.

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  • 新規利尿薬Ｍ１７０５５の生体内動態　第３報　　［｀１４´Ｃ］Ｍ１７０５５反復静脈内投与時のラットにおける血中濃度，分布および排せつ

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The plasma levels, tissue distribution and excretion of radioactivity were studied following repeated daily intravenous administration of [14C]M17055 to male rats at a dose of 0.3 mg/kg/day.<BR> 1. The plasma levels of radioactivity at 24 hours after each of 21 day-period of repeated administration to male rats were reached the steady state (6.90-8.87 ng eq./mL) by the 8th dosing. The calculated pharmacokinetic parameters were similar as those after the single administration.<BR> 2. Although the levels of radioactivity in all tissues at 24 hours after repeated administration to male rats rose according to the times of dosing, the rising rate was slow except for blood, lung, skin, digestive organs and their contents. At 1 hour after the 21st dosing, the radioactivity distributed highly to the liver and kidney as observed after the single administration. At 168 hours after the 21st dosing, the radioactivity tended to remain in highly perfused tissues, such as liver, kidney, spleen and lung. No tissue was identified in which the radioactivity retained for long period on the whole body autoradiograms.<BR> 3. Cumulative urinary and fecal excretions of radioactivity after 21 day repeated administration accounted for 58.17 and 37.35% of the total dose, respectively. The excretion rate in urine and feces well agreed to that after the single administration. The total excretion of radioactivity, including that present in the cage washing, accounted for 97.28% of the total dose.

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