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开蓬(十氯酮)在大鼠体内的分布与排泄

Distribution and excretion of chlordecone (Kepone) in the rat.

作者信息

Egle J L, Fernandez J B, Guzelian P S, Borzelleca J F

出版信息

Drug Metab Dispos. 1978 Jan-Feb;6(1):91-5.

PMID:74312
Abstract

Rats received a single, oral, 40-mg/kg dose of 14C-labeled chlordecone in a corn-oil solution. Initially the highest levels of radioactivity were found in the adrenal gland, liver, lung, and fat. While levels declined steadily in all tissues during the course of the study (182 days), the ratio of liver content to that of other tissues increased considerably. The blood half-life was 8.5 days for the first 4 weeks, 24 days for the next 8 weeks, and 45 days for the final 14 weeks, The amount excreted in the feces was 12.7% for the first 24 hr, 2.9% for the second, and 3.3% during the third 24-hr period. By 84 days 65.5% of the dose had been excreted by this route. Total urinary excretion of radioactivity for 84 days was 1.6%. These results indicate that chlordecone is well absorbed and distributed throughout the body, has a long half-life, and disappears more slowly from the liver than from other tissues. The majority of a dose is eliminated slowly in the feces with very little appearing in the urine. The findings are consistent with the expected pharmacokinetics of a chlorinated hydrocarbon, although there was less of a tendency to localize in fat than anticipated.

摘要

大鼠经口接受单剂量40毫克/千克的溶于玉米油溶液中的14C标记十氯酮。最初,在肾上腺、肝脏、肺和脂肪中发现放射性水平最高。在研究过程(182天)中,所有组织中的水平均稳步下降,但肝脏中的含量与其他组织中的含量之比显著增加。前4周血液半衰期为8.5天,接下来8周为24天,最后14周为45天。头24小时粪便排泄量为12.7%,第二个24小时为2.9%,第三个24小时期间为3.3%。到84天时,该途径已排泄65.5%的剂量。84天内放射性物质的总尿排泄量为1.6%。这些结果表明,十氯酮吸收良好并分布于全身,半衰期长,从肝脏中消失的速度比从其他组织中慢。大部分剂量通过粪便缓慢消除,尿液中出现的很少。这些发现与氯化烃预期的药代动力学一致,尽管在脂肪中定位的趋势比预期的要小。

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