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经口和经皮给予雌性Fischer 344大鼠2-乙基己醇后的代谢情况。

Metabolism of 2-ethylhexanol administered orally and dermally to the female Fischer 344 rat.

作者信息

Deisinger P J, Boatman R J, Guest D

机构信息

Biochemical Toxicology Section, Toxicological Sciences Laboratory, Eastman Kodak Company, Rochester, NY 14652-6272.

出版信息

Xenobiotica. 1994 May;24(5):429-40. doi: 10.3109/00498259409043246.

DOI:10.3109/00498259409043246
PMID:8079502
Abstract
  1. Excretion balance studies were conducted with 2-ethylhexanol (2-EH) in female Fischer 344 rats following single high (500 mg/kg) and low (50 mg/kg) oral doses of [14C]2-EH, following repeated oral dosing with unlabelled 2-EH at the low level, following dermal exposure for 6 h with a 1 g/kg applied dose of [14C]2-EH, and following a 1 mg/kg i.v. dose of [14C]2-EH. 2. The high, low and repeated low oral dose studies with 2-EH showed similar excretion balance profiles of [14C], with some evidence of metabolic saturation at the high dose. 3. No evidence of metabolic induction was seen following the repeated low oral dosing. 4. All of the oral doses were eliminated rapidly, predominantly in the urine during the first 24 h following dosing. 5. The dermal dosing resulted in only about 5% absorption of the 1 g/kg dose, with the major portion of the dose recovered unabsorbed from the dermal exposure cell at 6 h. 6. Urinary metabolites eliminated following the oral and dermal doses were predominantly glucuronides of oxidized metabolites of 2-EH, including glucuronides of 2-ethyladipic acid, 2-ethylhexanoic acid, 5-hydroxy-2-ethylhexanoic acid and 6-hydroxy-2-ethylhexanoic acid.
摘要
  1. 在用[¹⁴C]2 - 乙基己醇(2 - EH)单次高剂量(500毫克/千克)和低剂量(50毫克/千克)口服给药后,在用未标记的2 - EH进行低剂量重复口服给药后,在用1克/千克的[¹⁴C]2 - EH经皮暴露6小时后,以及在用1毫克/千克的[¹⁴C]2 - EH静脉注射给药后,对雌性Fischer 344大鼠进行了排泄平衡研究。2. 2 - EH的高、低和重复低口服剂量研究显示了[¹⁴C]的排泄平衡曲线相似,高剂量时有代谢饱和的一些证据。3. 重复低口服给药后未见代谢诱导的证据。4. 所有口服剂量均迅速消除,给药后的头24小时内主要通过尿液排泄。5. 经皮给药导致1克/千克剂量的吸收仅约5%,在6小时时,大部分剂量未被吸收而从经皮暴露池中回收。6. 口服和经皮给药后消除的尿代谢物主要是2 - EH氧化代谢物的葡糖醛酸苷,包括2 - 乙基己二酸、2 - 乙基己酸、5 - 羟基 - 2 - 乙基己酸和6 - 羟基 - 2 - 乙基己酸的葡糖醛酸苷。

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