好中球エラスターゼ阻害剤ＯＮＯ‐５０４６・Ｎａの体内動態（第１報）　ラットに単回静脈内投与した時の血中動態，分布および排せつ試験

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タイトル別名
  • Studies on the Metabolic Fate of Neutrophil Elastase Inhibitor ONO-5046Na (1): Plasma Concentration-profile, Distribution and Excretion after Single Intravenous Administration to Rats.

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The plasma concentration-time profile, distribution and excretion after a single intravenous administration of 14C-ONO-5046·Na were investigated in rats.<BR> 1. After intravenous bolus administration of 14C-ONO-5046·Na (0.1 ?? 100 mg/kg) to male rats, the elimination half life of radioactivity ranged from 163.61 to 192.72 min. AUC0-∞ increased in dose-dependent manner up to 1 mg/kg. Sex-related difference in pharmacokinetic parameter was not clearly observed at dose range of 0.1 ?? 100 mg/kg.<BR> 2. During 3 hr intravenous infusion of 14C-ONO-5046·Na at the doses of 0.1, land 10 mg/kg/hr to male rats, the plasma levels of radioactivity reached the steady-state levels within 1.5 hr. Plasma levels of radioactivity in the steady-state increased in dose-dependent manner, and the elimination half life ranged from 232.29 to 631.63 min.<BR> 3. At 30 min after intravenous bolus administration at the dose of 1 mg/kg to male and female rats, the radioactivity was distributed in whole body. Kidney, intestine and its contents, were the tissues highly concentrating radioactivity. Then radioactivity decreased to the level below detection limit in most tissues at 24 hr, and no marked residue in any tissue was found.<BR> 4. Within 24 hr after intravenous bolus ad ministration of 14C-ONO-5046·Na at the dose of 1 mg/kg to male rats, 24.0% and 73.1% of administered radioactivity were excreted into urine and feces, respectively. Total excretion rates into urine and feces within 72 hr was 99.4%. Within 24 hr after intravenous administration of 14C-ONO-5046·Na in female rats, the excretion rates into urine and feces were 90.2% and 8.2%, respectively. Sex-related difference was observed.<BR> 5. Within 2 hr after intravenous bolu s administration of 14C-ONO-5046·Na at the dose of 1 mg/kg, 33.0% and 14.0% of administered radioactivity were excreted into bile in male and female, respectively. Sex-related difference was observed. Cumulative excretion rates until 48 hr after administration were 35.9% and 15.4%, respectively. Almost all of radioactivity in bile was excreted until 2 hr after administration.<BR> 6. Re-absorption rate obtained from urinary and biliary excretion rate of recipient rats after administration to duodenum of the bile, which excreted after intravenous bolus administration of 14C-ONO-5046·Na at the dose of 1 mg/kg, were 38.9% in male rats, and 42.5% in female rats.

収録刊行物

  • 薬物動態

    薬物動態 12 (6), 551-565, 1997

    日本薬物動態学会

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