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在犬体内鉴定出一种N-氧化物是镇痛药盐酸O-(二乙氨基乙基)-4-氯苯甲醛肟的主要代谢产物。

Identification of an N-oxide as the major metabolite of the analgesic O-(diethylaminoethyl)-4-chlorobenzaldoxime hydrochloride in dogs.

作者信息

Kirkpatrick D, Weston K T, Hawkins D R, Chasseaud L F, Elsom L F

出版信息

Xenobiotica. 1977 Dec;7(12):747-55. doi: 10.3109/00498257709038704.

DOI:10.3109/00498257709038704
PMID:602249
Abstract
  1. After oral administration to dogs of the analgesic O-(diethylaminoethyl)-4-chloro[7-14C]benzaldoxime hydrochloride together with piperazine hydrochloride (2:1, w/w), at a dose of 4.5 mg/kg, the radioactivity was well absorbed and rapidly excreted. During 5 days, 81 percent of the dose (ca. 50 percent in 12 h) was excreted in urine and 10 percent in faeces. 2. Rates and routes of excretion of radioactivity were not altered in animals pre-treated with the drug for fourteen days. 3. Peak mean plasma concentrations of radioactivity (5.5 microgram equiv./ml) occurred at 90 min after an oral dose and were higher than those at 2 min following an equivalent intravenous (3.4 microgram equiv./ml) or rectal (4.0 microgram equiv./ml) dose which gave a max. at 45 min. 4. The drug was rapidly and extensively metabolized and no unchanged drug was detected in the plasma or urine. The major urinary metabolite was the N-oxide of the parent compound accounting for 34 percent and 23 percent dose excreted in the urine of males and females respectively during 12 h after administration.
摘要
  1. 给犬口服镇痛药O-(二乙氨基乙基)-4-氯[7-¹⁴C]苯甲醛肟盐酸盐与盐酸哌嗪(2:1,w/w),剂量为4.5mg/kg,放射性被很好地吸收并迅速排泄。在5天内,81%的剂量(12小时内约50%)经尿液排泄,10%经粪便排泄。2. 用该药物预处理14天的动物,放射性的排泄速率和途径未改变。3. 口服给药后90分钟出现放射性的血浆平均峰值浓度(5.5微克当量/毫升),高于等效静脉注射(3.4微克当量/毫升)或直肠给药(4.0微克当量/毫升)后2分钟的浓度,静脉注射和直肠给药的最大浓度出现在45分钟。4. 该药物迅速且广泛地代谢,血浆或尿液中未检测到未代谢的药物。主要的尿液代谢物是母体化合物的N-氧化物,给药后12小时内,分别占雄性和雌性尿液中排泄剂量的34%和23%。

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Xenobiotica. 1977 Dec;7(12):747-55. doi: 10.3109/00498257709038704.
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