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大鼠体内抗氧化剂乙氧喹(6-乙氧基-2,2,4-三甲基-1,2-二氢喹啉)的胆汁排泄及代谢产物研究。

Studies of the biliary excretion and metabolites of the antioxidant ethoxyquin, 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline in the rat.

作者信息

Skaare J U

出版信息

Xenobiotica. 1979 Nov;9(11):659-68. doi: 10.3109/00498257909042333.

DOI:10.3109/00498257909042333
PMID:532215
Abstract
  1. Biliary excretion and metabolites of ethoxyquin, and gastro-intestinal absorption of ethoxyquin were studied in rat. 2. An average of 28 and 36% of the dose of 14C following intragastric administration of [14C]ethoxyquin was recovered in the bile of bile-duct cannulated rats in 12 and 24 h, respectively. 3. By g.l.c.-mass spectrometry, 75 to 85% of the 14C excreted in the 12 h bile was identified as unchanged ethoxyquin, and the following metabolites were isolated and identified: 8-hydroxy-ethoxyquin, hydroxylated 8-hydroxy-ethoxyquin, 6-ethoxy-2,2,4-trimethyl-8-quinolone, hydroxylated 6-ethoxy-2,2,4-trimethyl-8-quinolone, 6-ethoxy-2,4-dimethylquinoline and 2,2,4-trimethyl-6-quinolone. 4. Three groups of rats were used in the biliary excretion experiments, and the effect of standardization of experimental conditions was demonstrated. Infusion of sodium taurocholate following bile-duct cannulation did not affect the biliary excretion kinetics of ethoxyquin. 5. Only about 3% of the radioactivity administered was absorbed from the gastrointestinal tract via the lymphatic pathway in thoracic-duct connulated rats within 24 h. It was concluded that ethoxyquin was absorbed primarily by the portal route.
摘要
  1. 研究了乙氧喹在大鼠体内的胆汁排泄、代谢产物以及胃肠道吸收情况。2. 分别在12小时和24小时内,经胆管插管的大鼠胆汁中回收了经胃内给予[14C]乙氧喹剂量的平均28%和36%的14C。3. 通过气相色谱-质谱联用分析,在12小时胆汁中排泄的14C的75%至85%被鉴定为未变化的乙氧喹,并且分离并鉴定了以下代谢产物:8-羟基-乙氧喹、羟基化的8-羟基-乙氧喹、6-乙氧基-2,2,4-三甲基-8-喹诺酮、羟基化的6-乙氧基-2,2,4-三甲基-8-喹诺酮、6-乙氧基-2,4-二甲基喹啉和2,2,4-三甲基-6-喹诺酮。4. 在胆汁排泄实验中使用了三组大鼠,并证明了实验条件标准化的效果。胆管插管后输注牛磺胆酸钠不影响乙氧喹的胆汁排泄动力学。5. 在胸导管插管的大鼠中,24小时内经胃肠道通过淋巴途径吸收的给予放射性仅约3%。得出的结论是,乙氧喹主要通过门静脉途径吸收。

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