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N-甲基甲酰胺在小鼠体内的药理学研究。

Studies of the pharmacology of N-methylformamide in mice.

作者信息

Brindley C, Gescher A, Harpur E S, Ross D, Slack J A, Threadgill M D, Whitby H

出版信息

Cancer Treat Rep. 1982 Nov;66(11):1957-65.

PMID:6814756
Abstract

When 400 mg/kg of 14C-methyl-labeled N-methylformamide (NMF) was injected ip into mice, the curve for plasma concentration of radioactivity versus time was superimposable on the curve obtained by measuring unmetabolized NMF with gas-liquid chromatography during the first 24 hrs. Radioactivity in plasma was measurable for 8 days after NMF administration, but NMF was not measurable by gas chromatography beyond 24 hrs after administration. Radioactivity was eliminated from the plasma after 60 hrs, with an apparent half-life of 71.1 hrs. Of the radioactivity injected with NMF, 73.6% was recovered in the urine in 24 hrs; 26.4% of this was unchanged NMF. Three percent of the administered radioactivity was exhaled as 14CO2 in 7 hrs at a constant rate of 0.007% per min. One urinary metablite was a stable precursor of formaldehyde, which decomposed to formaldehyde only after alkaline hydrolysis and may well be N-(hydroxymethyl)-formamide. The areas under the plasma concentration versus time curve were estimated after ip, iv, and oral administration of NMF. The bioavailability of NMF was 1.01 after oral administration and 1.10 after ip administration.

摘要

当以400毫克/千克的剂量将14C-甲基标记的N-甲基甲酰胺(NMF)腹腔注射到小鼠体内时,在前24小时内,放射性血浆浓度随时间变化的曲线与通过气液色谱法测量未代谢的NMF所获得的曲线重叠。NMF给药后8天血浆中的放射性均可测,但给药后24小时以上气相色谱法无法测出NMF。60小时后血浆中的放射性消除,表观半衰期为71.1小时。注射的NMF放射性中,73.6%在24小时内从尿液中回收;其中26.4%是未变化的NMF。给药放射性的3%在7小时内以每分钟0.007%的恒定速率作为14CO2呼出。一种尿代谢物是甲醛的稳定前体,仅在碱性水解后分解为甲醛,很可能是N-(羟甲基)-甲酰胺。在腹腔注射、静脉注射和口服NMF后,估计了血浆浓度随时间变化曲线下的面积。口服NMF后的生物利用度为1.01,腹腔注射后为1.10。

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