Absorption, distribution, metabolism, and excretion of [1-14C]-perfluorohexanoate ([14C]-PFHx) in rats and mice
Absorption, distribution, metabolism, and excretion of [1-14C]-perfluorohexanoate ([14C]-PFHx) in rats and mice
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DOI：
10.1016/j.tox.2011.02.004
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发表时间：
2011-04-28
期刊：
影响因子：
4.5
通讯作者：
Loveless, Scott E.
中科院分区：
文献类型：
--
作者：
Gannon, Shawn A.;Johnson, Terry;Loveless, Scott E.
在单次给药或连续14次给药后，评价了大鼠和小鼠经口给予2或100 mg/kg [1-C-14]-PFHx的吸收、组织分布、消除和代谢。在2和100 mg/kg剂量水平下，雄性大鼠达到最大浓度（C-max）的时间较短，为30 min，雌性大鼠为15 min，证明大鼠吸收迅速。雄性（1.5-1.7 h）的血浆消除半衰期略长于雌性（0.5-0.7 h）。小鼠中的吸收也很快，最大血浆浓度出现在给药后15 - 30 min之间。雄性和雌性小鼠之间的最大浓度没有明显差异（8 μ g当量/ml）。2 mg/kg时为2.5g;与350 μ g当量/ g，100 mg/kg）。主要消除途径为尿液。PFHx在大鼠或小鼠肝细胞中未代谢，在两种啮齿动物经口给药后也未观察到任何代谢产物。在24小时内，基本上100%的剂量通过尿液消除，表明PFHx易于吸收，生物利用度接近100%，即使剂量高达100 mg/kg。每日给药14天后，消除途径和程度保持不变。在给药后三个时间点（大鼠：0.5、2和24 h;小鼠：0.25、1和24 h）采集组织，以研究2或100 mg/kg单次给药后PFHx的组织清除动力学。在除皮肤外的所有组织中，两个种属的两种性别动物在给药后24 h均无法定量测定PFHx。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The absorption, tissue distribution, elimination, and metabolism of [1-C-14]-PFHx in rats and mice dosed orally at 2 or 100 mg/kg was evaluated following a single dose or after 14 consecutive doses. Absorption was rapid in rats as evidenced by a short time to maximum concentration (C-max) of 30 min in male rats and 15 min in female rats at both the 2 and 100 mg/kg dose level. The plasma elimination half-life was somewhat longer in males (1.5-1.7 h) than in females (0.5-0.7 h). Absorption in the mouse was also rapid with the maximum plasma concentration occurring between 15 and 30 min after dosing. The maximum concentration was not appreciably different between male and female mice (8 mu g equiv./g at 2 mg/kg; similar to 350 mu g equiv./g at 100 mg/kg). The primary route of elimination was via the urine. PFHx was not metabolized in rat or mouse hepatocytes, nor were any metabolites observed after oral dosing in either rodent species. Essentially 100% of the dose was eliminated in urine within 24h demonstrating that PFHx is readily absorbed and bioavailability approaches 100%, even at a dose as high as 100 mg/kg. The route and extent of elimination was unchanged after 14 days of daily dosing. Tissues were collected at three time points (rat: 0.5, 2, and 24h; mice: 0.25, 1, and 24h) after dosing to investigate the tissue clearance kinetics of PFHx following a single dose at 2 or 100 mg/kg. In all tissues except skin, PFHx was not quantifiable 24 h after dosing in both sexes of the two species. (C) 2011 Elsevier Ireland Ltd. All rights reserved.