TOXICOKINETICS OF PERMETHRIN IN THE RAT
TOXICOKINETICS OF PERMETHRIN IN THE RAT
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DOI：
10.1016/0041-008x(91)90284-l
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发表时间：
1991-08-01
影响因子：
3.8
通讯作者：
BRINGAS, P
中科院分区：
文献类型：
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作者：
ANADON, A;MARTINEZLARRANAGA, MR;BRINGAS, P
在雄性Sprague-Dawley大鼠中研究了单次经口给予460 mg/kg和静脉给予46 mg/kg氯菊酯后的毒代动力学。采集经口和静脉给药后的系列血液样本，以及经口给药后的脑、延髓、坐骨神经和肝脏样本。血浆，下丘脑，小脑，额叶皮质，尾壳核，海马，延髓，坐骨神经，和肝脏浓度的氯菊酯及其代谢产物，间苯氧基苯甲醇和间苯氧基苯甲酸，通过高效液相色谱法测定。氯菊酯的血浆曲线可用二室开放模型描述。对于氯菊酯，静脉给药后的消除半衰期（t1 2β）和血浆中的平均滞留时间分别为8.67和11.19小时，口服给药后分别为12.37和17.77小时。氯菊酯的血浆清除率不受给药浓度和给药途径的影响，可达0.058L/hr，一次口服后吸收缓慢，Tmax为3.52hr，最大血药浓度为49.46 μg/ml。氯菊酯的口服生物利用度为60.69%。氯菊酯代谢物的血浆浓度-时间数据以及氯菊酯及其代谢物口服给药后的组织浓度-时间数据符合一室开放模型。海马、延髓、额叶皮质和坐骨神经中氯菊酯的消除半衰期（t1 2 el）（分别为23.10、22.36、13.86和16.27 h）大于血浆中氯菊酯的消除半衰期（t1 2β，12.37 h）。小脑、海马、尾壳核、额叶皮质、下丘脑和坐骨神经中的二氯苯菊酯最大量分别约为血浆中的1.5、2、2、2.7、4.8和7.5倍，表明拟除虫菊酯通过神经组织本身蓄积。组织/血浆浓度曲线下面积比（分别为1.16、3.71、1.57、4.27、3.48和8.77）也反映了氯菊酯的神经组织蓄积。给药后48 h，在血浆和所有选定组织中检测到氯菊酯、间苯氧基苄醇和间苯氧基苯甲酸的代谢物，表明可能存在组织代谢和血液扩散的组合。
The toxicokinetics of permethrin after single 460 mg/kg oral and 46 mg/kg intravenous doses were studied in male Sprague-Dawley rats. Serial blood samples after oral and intravenous dosage, and brain, medulla oblongata, sciatic nerve, and liver samples after oral administration were collected. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, sciatic nerve, and liver concentrations of permethrin and its metabolites, m-phenoxybenzyl alcohol and m-phenoxybenzoic acid, were determined by a high-performance liquid chromatographic assay. The permethrin plasma profile could be adequately described by a two-compartment open model. For permethrin, the elimination half-life (t1 2β) and the mean residence time from plasma were 8.67 and 11.19 hr after iv and 12.37 and 17.77 hr after po administration. The total plasma clearance was not influenced by dose concentration or route and reached a value of 0.058 liter/hr. After the single oral dose, permethrin was absorbed slowly with a Tmaxof 3.52 hr. The maximum plasma concentration was 49.46 μg/ml. The oral bioavailability of permethrin was found to be 60.69%. The plasma concentration-time data for permethrin metabolites as well as the tissue concentration-time data for permethrin and its metabolites after an oral dose of permethrin were found to fit a one-compartment open model. The elimination half-life (t1 2 el) of permethrin was greater for the hippocampus, medulla oblongata, frontal cortex, and sciatic nerve (23.10, 22.36, 13.86, and 16.27 hr, respectively) than for plasma (t1 2β, 12.37 hr). The maximum amounts of permethrin in cerebellum, hippocampus, caudate putamen, frontal cortex, hypothalamus, and sciatic nerve were about 1.5, 2, 2, 2.7, 4.8, and 7.5 times higher than in plasma, respectively, indicating an accumulation of pyrethroid by nervous tissue itself. Nervous tissue accumulation of permethrin was also reflected by the area under the concentration curve ratios of tissue/plasma (1.16, 3.71, 1.57, 4.27, 3.48, and 8.77, respectively). The metabolites of permethrin, m-phenoxybenzyl alcohol and m-phenyxybenzoic acid, were detected in plasma and in all selected tissues for 48 hr after dosing, suggesting that a combination of metabolism by the tissues and diffusion into it from the blood may be present.