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14C-1,3-二氯丙烯在Fischer 344大鼠和B6C3F1小鼠体内的药代动力学与代谢

Pharmacokinetics and metabolism of 14C-1,3-dichloropropene in the Fischer 344 rat and the B6C3F1 mouse.

作者信息

Bartels M J, Hansen S C, Thornton C M, Brzak K A, Mendrala A L, Dietz F K, Kastl P J

机构信息

Health and Environmental Research & Consulting Department, The Dow Chemical Co., Midland, MI 48674, USA.

出版信息

Xenobiotica. 2004 Feb;34(2):193-213. doi: 10.1080/00498250310001636859.

Abstract
  1. 14C-1,3-dichloropropene (14C-DCP) is rapidly absorbed and eliminated in both the male F344 rat and B6C3F1 mouse following oral administration of 1 or 50 mg kg(-1) (rat) or 1 or 100 mg kg(-1) (mouse). 2. It is extensively metabolized in both species. Urinary excretion was the major route of elimination, accounting for 50.9-61.3 and 62.5-78.6% of the administered dose in rat and mouse, respectively. 3. Urinary elimination half-lives ranged from 5 to 6 h (rat) and from 7 to 10 h (mouse). Elimination via faeces or as 14CO2 accounted for 14.5-20.5 and 13.7-17.6% of the administered dose, respectively. 4. Metabolites arising from glutathione conjugation account for 36-55 and 48-50% of the administered dose in excreted from rats and mice, respectively. Hydrolysis of the 3-chloro moiety of DCP accounted for 24-37 and 29% of the dose administered to rats and mice, respectively. Two novel dimercapturic acid conjugates were also identified at low levels that might arise via initial hydrolysis of DCP or of epoxidation of DCP-glutathione conjugate or of DCP itself. Structural confirmation of these dimercapturates was obtained via analysis of deuterium retention from D4-DCP in the male F344 rat. 5. Only quantitative differences are seen between the overall metabolic profile of DCP in these two species.
摘要
  1. 给雄性F344大鼠口服1或50mg/kg(大鼠)、给B6C3F1小鼠口服1或100mg/kg(小鼠)的14C - 1,3 - 二氯丙烯(14C - DCP)后,它能在这两种动物体内迅速吸收和消除。2. 它在这两个物种中都被广泛代谢。尿排泄是主要的消除途径,分别占大鼠和小鼠给药剂量的50.9 - 61.3%和62.5 - 78.6%。3. 尿消除半衰期在大鼠中为5至6小时,在小鼠中为7至10小时。经粪便或作为14CO2消除分别占给药剂量的14.5 - 20.5%和13.7 - 17.6%。4. 谷胱甘肽结合产生的代谢物分别占大鼠和小鼠排泄给药剂量的36 - 55%和48 - 50%。DCP的3 - 氯部分水解分别占给予大鼠和小鼠剂量的24 - 37%和29%。还鉴定出两种低水平的新型二巯基尿酸结合物,它们可能通过DCP的初始水解、DCP - 谷胱甘肽结合物的环氧化或DCP本身的环氧化产生。通过分析雄性F344大鼠中D4 - DCP的氘保留情况,对这些二巯基尿酸进行了结构确认。5. 在这两个物种中,DCP的总体代谢谱仅存在定量差异。

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