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首页> 外文期刊>薬物動態 >Studies on the metabolic faTE OF m17055, a novel diuretic(5):pharmacokinetics and pharmacodynamics of unchanged drug in rat and dog after intravenous administration of M17055
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Studies on the metabolic faTE OF m17055, a novel diuretic(5):pharmacokinetics and pharmacodynamics of unchanged drug in rat and dog after intravenous administration of M17055

机译：M17055的代谢命运，一种新型利尿（5）：静脉施用M17055后大鼠和狗的药代动力学和药效学和药效学

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摘要

The pharmacokinetics and pharamcodynamics of M17055,a novel diuretic were studied affter a single intravenous administration to rats and dogs,the two species used in the pharmacological and to xicologicla studies.No gender dependent resposne to systemic exposure was observed at the high dose levelin rats,in agreement with the determined LD_(50).A gender difference in urinary excretion of M17055,however,was clearly observed in rats.The slower elimination and the lower total body clearance (CLtot) values of M17055 in dogs reflect the difference of the no-effect elvel (NOEL)between rats (0.1 mg/kg) and dogs (0.03 mg/kg) well.The diuretic resposne was well correlated with the urinary M17055 excretion rae by fitting to a singmoid E_(max) model in both rats and dogs.The derived ER-(50) value of M17055 in dogs was approximately 10 times less than that reported forfurosemide,suggesting that the intrinsic potency of M17055 is equal to or higher than those of other powerful loop diuretics.Although diuretic sensitivity was considered to be lower in dogs than in rats,the higher amount of M17055 reaching the dog kidney is likely to compensate for this.The diuretic response infemale rats was predictable by using the pharmacodynamic parameters derived from male rats.These results show that the apparent high diuretic potency and the other pivotal observations for M17055 found in the pharmacological and toxicological studies can be rationalized by the pharmacokinetic and pharmacodynamic properties of the unchanged compound.
机译：M17055的药代动力学和磷脂动力学，一种新型利尿剂，研究了对大鼠和狗的单一静脉内给药，药理学和XICOLOGICLA研究中使用的两种物种。在高剂量水平大鼠中观察到性别依赖于全身暴露于全身暴露于全身暴露。然而，与确定的LD_（50）的LD_（50）。然而，在大鼠中清楚地观察到M17055的尿排泄中的性别差异。慢速消除较慢和狗M17055的较低总体清除（CLTOT）值反映了NO的差异 - 大鼠（0.1mg / kg）和狗（0.03mg / kg）井之间的elvel（noel）。利尿剂resposne与尿m17055排泄饲料良好，通过拟合到两只大鼠的单曲e_（max）模型和狗的衍生Er-（50）犬M17055的价值比报告的对核胺的少数少10倍，表明M17055的内在效力等于或高于其他强大的环路利尿剂.althou GH利尿敏感性被认为是低于大鼠的狗的较低量，达到狗肾的M17055较高的M17055可能会弥补这一点。利尿剂响应患者通过使用雄性大鼠衍生的药效学参数来预测可预测。这些结果表明在药理学和毒理学研究中发现的明显高利尿效力和用于M17055的其他枢轴观察可以通过不变化合物的药代动力学和药物动力学性能合理化。

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  • 来源
    《薬物動態》 |2002年第3期|共7页
  • 作者

    Hiroyuki Nakajima; Hiroyasu Naba; Takeshi Nakanishi; Kiyohiko Nakai; Takanori Watanabe; Nobuo Ohzawa;

  • 作者单位

    Drug Metabolism and Pharmacokinetics Laboratory Research Center mochida Pharmaceutical Co. Ltd. Gotemba Shizuoka Japan;

    Drug Metabolism and Pharmacokinetics Laboratory Research Center mochida Pharmaceutical Co. Ltd. Gotemba Shizuoka Japan;

    Drug Metabolism and Pharmacokinetics Laboratory Research Center mochida Pharmaceutical Co. Ltd. Gotemba Shizuoka Japan;

    Drug Metabolism and Pharmacokinetics Laboratory Research Center mochida Pharmaceutical Co. Ltd. Gotemba Shizuoka Japan;

    Drug Metabolism and Pharmacokinetics Laboratory Research Center mochida Pharmaceutical Co. Ltd. Gotemba Shizuoka Japan;

    Drug Metabolism and Pharmacokinetics Laboratory Research Center mochida Pharmaceutical Co. Ltd. Gotemba Shizuoka Japan;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 药学;制药化学工业;
  • 关键词

    m17055; diuretic; systemic exposure; urinary excretion rate; pharmacokinetics; pharamcodynamics;

    机译：M17055;利尿剂;全身暴露;尿排泄率;药代动力学;斑抗性动力学;

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