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大鼠体内DDE的分布与消除动力学

Kinetics of distribution and elimination of DDE in rats.

作者信息

Mühlebach S, Moor M J, Wyss P A, Bickel M H

机构信息

Department of Pharmacology, University of Berne, Switzerland.

出版信息

Xenobiotica. 1991 Jan;21(1):111-20. doi: 10.3109/00498259109039455.

Abstract
  1. Rats were given single i.v. doses of 14C-DDE, and total drug (14C) and unchanged DDE (g.l.c.) were measured for up to 14 days in blood, tissues, and excreta. The 14C recoveries amounted to 90.0 +/- 10.8 (SD) % dose. 2. DDE underwent redistribution from blood to liver, muscle, skin and, ultimately, adipose tissue. The tissue/blood concentration ratios were 6 for liver and muscle, 35 for skin, 400 for adipose tissue. Concentrations in blood and lean tissues declined biphasically with beta-half-lives of 8-12 days. The half-lives for adipose tissue and total body burden were larger by one order of magnitude. However, due to the increase of adipose tissue mass with time, the amount of DDE stored therein remained constant at almost 60% dose. 3. Except for liver, no substantial metabolite concentrations in tissues were found. In particular, lipophilic metabolites were clearly absent. Thus, tissue kinetics and storage are controlled by unchanged DDE. 4. Of a given dose of DDE, 31% was excreted in the faeces as polar metabolites within 14 days, and 3-4% dose as DDE. Urinary excretion was negligible. The beta-half-life of faecal excretion was equal to the one in blood and lean tissues. It is concluded that excretion is limited by the slow formation of polar metabolites of DDE.
摘要
  1. 给大鼠静脉注射单次剂量的14C-DDE,在长达14天的时间内测定血液、组织和排泄物中的总药物(14C)和未变化的DDE(气相色谱法)。14C的回收率相当于剂量的90.0±10.8(标准差)%。2. DDE从血液重新分布到肝脏、肌肉、皮肤,最终到脂肪组织。组织/血液浓度比,肝脏和肌肉为6,皮肤为35,脂肪组织为400。血液和瘦组织中的浓度呈双相下降,β半衰期为8 - 12天。脂肪组织和全身负荷的半衰期大一个数量级。然而,由于脂肪组织质量随时间增加,其中储存的DDE量几乎保持在剂量的60%不变。3. 除肝脏外,在组织中未发现大量代谢物浓度。特别是,明显不存在亲脂性代谢物。因此,组织动力学和储存由未变化的DDE控制。4. 给定剂量的DDE中,31%在14天内以极性代谢物的形式随粪便排出,3 - 4%的剂量以DDE形式排出。尿液排泄可忽略不计。粪便排泄的β半衰期与血液和瘦组织中的相等。结论是排泄受DDE极性代谢物形成缓慢的限制。

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