二异丙基甲基膦酸酯在水貂和大鼠体内的代谢比较

The comparative metabolism of diisopropyl methylphosphonate in mink and rats.

作者信息

Weiss D J, Geary R S, Wustenberg W, Bucci T J, Perman V, Baumel I P, Dacre J C

机构信息

Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108.

出版信息

Arch Environ Contam Toxicol. 1994 Oct;27(3):420-5. doi: 10.1007/BF00213181.

DOI:10.1007/BF00213181

PMID:7944557

Abstract

This study reports the metabolism of carbon-14labeled diisopropyl methylphosphonate (DIMP) in mink and rats, undertaken to better understand the dose-related mortality reported for mink in a previous study. In both male and female mink and rats, DIMP was rapidly absorbed after oral administration; it was metabolized by a saturable pathway to a single metabolite, isopropyl methylphosphonate (IMPA), which was rapidly excreted, primarily in the urine (90%). Fecal radioactivity, also identified as IMPA, was 1.7-3.1% of the administered dose. Female rats had a slower rate of conversion of DIMP to IMPA and less total excretion of IMPA than male rats. Metabolism of DIMP administered intravenously was not very different from that given orally in both species. These data indicate that mink absorb, metabolize, and excrete DIMP (as IMPA) in a manner very similar to mice, rats, and dogs.

摘要

本研究报告了碳 - 14标记的甲基膦酸二异丙酯（DIMP）在水貂和大鼠体内的代谢情况，开展该研究是为了更好地理解先前一项研究中报告的水貂与剂量相关的死亡率。在雄性和雌性水貂及大鼠中，口服给药后DIMP均被快速吸收；它通过一条可饱和途径代谢为单一代谢物甲基膦酸异丙酯（IMPA），IMPA迅速排泄，主要通过尿液（90%）。粪便中的放射性物质，也被鉴定为IMPA，占给药剂量的1.7 - 3.1%。雌性大鼠将DIMP转化为IMPA的速率比雄性大鼠慢，且IMPA的总排泄量也比雄性大鼠少。在这两个物种中，静脉注射DIMP的代谢情况与口服给药的代谢情况没有太大差异。这些数据表明，水貂吸收、代谢和排泄DIMP（以IMPA形式）的方式与小鼠、大鼠和狗非常相似。