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异丙醇在F-344大鼠和B6C3F1小鼠体内的处置及药代动力学

Disposition and pharmacokinetics of isopropanol in F-344 rats and B6C3F1 mice.

作者信息

Slauter R W, Coleman D P, Gaudette N F, McKee R H, Masten L W, Gardiner T H, Strother D E, Tyler T R, Jeffcoat A R

机构信息

International Research and Development Corporation, Mattawan, Michigan 49071.

出版信息

Fundam Appl Toxicol. 1994 Oct;23(3):407-20. doi: 10.1006/faat.1994.1122.

Abstract

The absorption, metabolism, disposition, and excretion of isopropanol (IPA) were studied in male and female rats and mice. Animals were exposed by i.v. (300 mg/kg) and inhalation (500 and 5000 ppm for 6 hr) routes; additionally, IPA was given by gavage to rats only in single and multiple 300 and 3000 mg/kg doses. In the rat approximately 81-89% of the administered dose was exhaled (as acetone, CO2, and unmetabolized IPA); approximately 76% of the dose in mice was exhaled after i.v. bolus but 92% was exhaled following inhalation. Approximately 3-8% of the administered dose was excreted in urine as IPA, acetone, and a metabolite tentatively identified as isopropyl glucuronic acid. Small amounts of radiolabel were found in feces and in the carcass. There were no major differences in the rates or routes of excretion observed either between sexes or between routes of administration. Additionally, repeated exposure had no effect on excretion. However, both the route of administration and the exposure or dose level influenced the form in which material was exhaled. Following exposure to 5000 ppm, a greater percentage of unmetabolized IPA was recovered in the expired air than following exposure to 500 ppm, implying saturation of metabolism.

摘要

在雄性和雌性大鼠及小鼠中研究了异丙醇(IPA)的吸收、代谢、分布和排泄情况。动物通过静脉注射(300毫克/千克)和吸入(500和5000 ppm,持续6小时)途径暴露;此外,仅对大鼠进行灌胃,单次和多次给予300和3000毫克/千克剂量的IPA。在大鼠中,约81 - 89%的给药剂量通过呼气排出(以丙酮、二氧化碳和未代谢的IPA形式);静脉推注后,小鼠中约76%的剂量通过呼气排出,但吸入后为92%。约3 - 8%的给药剂量以IPA、丙酮和一种暂定为异丙基葡萄糖醛酸的代谢物形式经尿液排出。在粪便和 carcass 中发现少量放射性标记物。在性别之间或给药途径之间,未观察到排泄速率或途径的主要差异。此外,重复暴露对排泄无影响。然而,给药途径以及暴露或剂量水平会影响呼出物质的形式。暴露于5000 ppm后,呼出空气中回收的未代谢IPA百分比高于暴露于500 ppm后,这意味着代谢饱和。 (注:carcass 原意为动物尸体,这里结合语境可能是指动物机体等类似意思,但不太明确其确切指代,需结合更完整背景信息理解)

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