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50毫克/千克体重的[2,3-¹⁴C]丙烯酰胺单次口服剂量在白来航鸡体内的毒代动力学。

Toxicokinetics of a single 50 mg/kg oral dose of [2,3-14C]acrylamide in White Leghorn hens.

作者信息

Blumenthal G M, Abdel-Rahman A A, Wilmarth K R, Friedman M A, Abou-Donia M B

机构信息

Department of Pharmacology, Duke University, Medical Center, Durham, North Carolina 27710, USA.

出版信息

Fundam Appl Toxicol. 1995 Aug;27(1):149-53. doi: 10.1006/faat.1995.1118.

DOI:10.1006/faat.1995.1118
PMID:7589925
Abstract

A single oral dose of [2,3-14C]acrylamide (50 mg/kg) was administered in water to adult white leghorn hens. Seven groups of three hens were euthanized between 2 and 120 hr after administration. Within 12 hr, the hens excreted 70% of the administered dose, and more than 99% within 48 hr. Blood, plasma, liver, and muscle contained the greatest percentage of administered dose at 4 hr after dosing. Less than 0.02% of the administered dose appeared in brain at any time. Radiolabel accumulated in the eggs, with 0.52% of the administered dose accumulated within 5 days. Binding of radiolabel to erythrocytes was minimal. Elimination of radiolabel from all tissues was biphasic. Terminal elimination half-lives for 14C were longer than 10 days, at which time less than 0.2% of the administered dose remains in the tissues. Distribution half-lives for 14C were longest for whole blood and shortest for kidney. Radioactivity in the blood and plasma reached a peak at between 4 and 12 hr. Most of this radioactivity was identified as acrylamide, which disappeared biexponentially with terminal elimination half-lives longer than 10 days. Distribution half-lives for acrylamide were longest in brain and shortest in whole blood. These results show that orally administered acrylamide is poorly absorbed and rapidly eliminated from hens and accumulates in their eggs in a nonextractable form.

摘要

给成年白来航母鸡经口灌胃一剂[2,3-¹⁴C]丙烯酰胺(50毫克/千克),溶剂为水。给药后2至120小时内,将七组每组三只母鸡安乐死。给药后12小时内,母鸡排出了给药剂量的70%,48小时内排出了超过99%。给药后4小时,血液、血浆、肝脏和肌肉中所含给药剂量的百分比最高。在任何时候,给药剂量中出现在脑中的比例都不到0.02%。放射性标记物在鸡蛋中蓄积,给药剂量的0.52%在5天内蓄积。放射性标记物与红细胞的结合极少。所有组织中放射性标记物的消除呈双相性。¹⁴C的终末消除半衰期超过10天,此时组织中残留的给药剂量不到0.2%。¹⁴C在全血中的分布半衰期最长,在肾脏中最短。血液和血浆中的放射性在4至12小时达到峰值。大部分这种放射性被鉴定为丙烯酰胺,其以双指数形式消失,终末消除半衰期超过10天。丙烯酰胺在脑中的分布半衰期最长,在全血中最短。这些结果表明,经口给予的丙烯酰胺在母鸡体内吸收较差且迅速消除,并以不可提取的形式在鸡蛋中蓄积。

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