口服、静脉注射和经皮给药后大鼠体内甲乙酮肟的处置情况。

Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration.

Burka L T, Black S R, Mathews J M

Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Xenobiotica. 1998 Oct;28(10):1005-15. doi: 10.1080/004982598239065.

Abstract

The disposition of 14C-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49%) in decreasing percentage as the dose increased. Excretion in urine (13-26%) and as volatiles (5-18%) increased as the dose increased. Five to 6% of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8%) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4%, respectively. About 7% of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26% of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles.

摘要

研究了雄性F344大鼠经口、静脉注射（i.v.）和皮肤给药后14C-甲乙酮肟（MEKO）的处置情况。2. 经口给予2.7、27和270 mg/kg剂量后，主要以二氧化碳形式排出（71%-49%），随着剂量增加，排出百分比降低。尿液排出量（13%-26%）和挥发性物质排出量（5%-18%）随着剂量增加而增加。72小时后，5%-6%的剂量残留在主要组织中。3. 静脉注射2.7 mg/kg剂量后，也主要以二氧化碳形式排出（48.8%），尿液排出和呼出挥发性物质分别占21.4%和11.4%。72小时后，约7%的给药放射性残留在组织中。4. 皮肤给药后，2.7和270 mg/kg剂量分别有13%和26%被吸收。在放入代谢笼之前，剂量部位的挥发可能是吸收低的原因。5. MEKO被生物转化为至少五种极性代谢物，这些代谢物只能通过阴离子交换色谱部分分离。用葡糖醛酸酶孵育可改变尿液代谢谱，但硫酸酯酶则不能。甲乙酮是挥发性物质的主要成分。