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大鼠和小鼠经口、静脉和皮肤给药后二乙醇胺的吸收、代谢及处置情况。

Diethanolamine absorption, metabolism and disposition in rat and mouse following oral, intravenous and dermal administration.

作者信息

Mathews J M, Garner C E, Black S L, Matthews H B

机构信息

Center for Bioorganic Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA.

出版信息

Xenobiotica. 1997 Jul;27(7):733-46. doi: 10.1080/004982597240316.

DOI:10.1080/004982597240316
PMID:9253149
Abstract
  1. The disposition of [14C]diethanolamine (DEA) (1) was determined in rat after oral, i.v. and dermal administration, and in mouse after dermal administration. 2. Oral administration of DEA to rat was by gavage of 7 mg/kg doses once and after daily repeat dosing for up to 8 weeks. Oral doses were well absorbed but excreted very slowly. DEA accumulated to high concentrations in certain tissues, particularly liver and kidney. The steady-state of bioaccumulation was approached only after several weeks of repeat oral dosing, and the half-life of elimination was approximately 1 week. 3. DEA was slowly absorbed through the skin of rat (3-16% in 48 h) after application of 2-28 mg/kg doses. Dermal doses ranging from 8 to 80 mg/kg were more readily absorbed through mouse skin (25-60%) in 48 h of exposure, with the percent of the applied dose absorbed increasing with dose. 4. Single doses (oral or i.v.) of DEA were excreted slowly in urine (c. 22-25% in 48 h) predominantly as the parent compound. There was minimal conversion to CO2 or volatile metabolites in breath. The profile of metabolites appearing in urine changed after several weeks of repeat oral administration, with significant amounts of N-methylDEA and more cationic metabolites appearing along with unchanged DEA.
摘要
  1. 测定了[14C]二乙醇胺(DEA)(1)经口、静脉注射和皮肤给药后在大鼠体内的处置情况,以及经皮肤给药后在小鼠体内的处置情况。2. 给大鼠经口给予DEA的方式为,一次性灌胃7 mg/kg剂量,并在每日重复给药长达8周后进行。口服剂量吸收良好,但排泄非常缓慢。DEA在某些组织中积累至高浓度,尤其是肝脏和肾脏。仅在重复口服给药数周后才接近生物累积的稳态,消除半衰期约为1周。3. 给大鼠皮肤涂抹2 - 28 mg/kg剂量后,DEA经皮肤缓慢吸收(48小时内吸收3 - 16%)。在暴露48小时内,8至80 mg/kg的皮肤剂量经小鼠皮肤吸收更易(25 - 60%),吸收的给药剂量百分比随剂量增加而增加。4. 单剂量(经口或静脉注射)的DEA在尿液中排泄缓慢(48小时内约排泄22 - 25%),主要以母体化合物形式存在。呼吸中转化为二氧化碳或挥发性代谢物的量极少。重复口服给药数周后,尿液中出现的代谢物谱发生变化,除未变化的DEA外,还出现大量N - 甲基DEA和更多阳离子代谢物。

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