Anadón A, Martinez-Larrañaga M R, Fernandez-Cruz M L, Diaz M J, Fernandez M C, Martinez M A
Department of Toxicology, CSIC, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain.
Toxicol Appl Pharmacol. 1996 Nov;141(1):8-16. doi: 10.1006/taap.1996.0254.
The toxicokinetics of deltamethrin and its metabolite 4'-HO-deltamethrin after single doses of 26 mg of deltamethrin/kg (oral) or 1.2 mg of deltamethrin/kg (intravenous) were studied in male Wistar rats. Serial blood samples were obtained after oral and intravenous administration. Brain, vas deferens, and anococcygeus tissue samples were also obtained after oral administration. Plasma, hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, vas deferens, and anococcygeus concentrations of deltamethrin and 4'-HO-deltamethrin were determined by a high-performance liquid chromatographic assay. The deltamethrin and 4'-HO-deltamethrin plasma profiles could be adequately described by a two-compartment open model. For deltamethrin and 4'-HO-deltamethrin, the elimination half-lives (t1/2 theta) from plasma were 33.0 and 25.67 hr after iv and 38.50 and 30.13 hr after po administration of deltamethrin parent compound. The apparent volume of distribution [V alpha(area)] and volume of distribution at steady state [V d(m)] for deltamethrin were 5.33 and 2.04 liters, respectively, after iv administration, suggesting a considerable diffusion of the pyrethroid into tissue. The total plasma clearance of deltamethrin was the same for both the oral and the iv routes-0.11 liter/hr. After the single oral dose, deltamethrin was rapidly absorbed with a Tmax of 1.83 hr. The maximum plasma concentrations of deltamethrin and 4'-HO-deltamethrin were 0.46 and 0.26 microgram/ml. The maximum plasma concentration of 4'-HO-deltamethrin was achieved at 3.29 hr. The oral bioavailability of deltamethrin was found to be 14.43%. The tissue concentration time data for deltamethrin and its metabolite 4'-HO-deltamethrin were found to fit a one-compartment open model. Considerable concentrations of deltamethrin and 4'-HO-deltamethrin were found in the hypothalamus, cerebellum, frontal cortex, caudate putamen, hippocampus, medulla oblongata, vas deferens, and anococcygeus tissues. The elimination half-lives (t1/2 el) for both deltamethrin and 4'-HO-deltamethrin were somewhat smaller for the cerebellum, frontal cortex, caudate putamen, medulla oblongata, vas deferens, and anococcygeus tissues (range, 18-33 hr for deltamethrin and 15-28 hr for 4'-HO-deltamethrin) than for plasma (t1/2 el, 38.50 and 30.13 hr, respectively). Exceptions were seen for the hypothalamus and hippocampus in which the t1/2et's for deltamethrin were 40.76 and 38.50 hr, respectively. Nervous tissue accumulation of deltamethrin and its metabolite 4'-HO-deltamethrin was evidenced by the tissue/plasma area under the concentration (AUC) versus time curve ratios. The ratios of AUCtissue/AUCplasma for deltamethrin were 2.32 in medulla oblongata, 295.30 in hypothalamus, and intermediate in other tissues.
在雄性Wistar大鼠中研究了单剂量26 mg溴氰菊酯/千克（口服）或1.2 mg溴氰菊酯/千克（静脉注射）后溴氰菊酯及其代谢物4'-羟基溴氰菊酯的毒代动力学。口服和静脉给药后采集系列血样。口服给药后还采集脑、输精管和尾骨肌组织样本。采用高效液相色谱法测定血浆、下丘脑、小脑、额叶皮质、尾状核、海马、延髓、输精管和尾骨肌中溴氰菊酯和4'-羟基溴氰菊酯的浓度。溴氰菊酯和4'-羟基溴氰菊酯的血浆曲线可用二室开放模型充分描述。对于溴氰菊酯和4'-羟基溴氰菊酯，静脉注射溴氰菊酯母体化合物后，血浆消除半衰期（t1/2θ）分别为33.0和25.67小时，口服给药后分别为38.50和30.13小时。静脉注射后，溴氰菊酯的表观分布容积[Vα(area)]和稳态分布容积[Vd(m)]分别为5.33和2.04升，表明拟除虫菊酯大量扩散到组织中。溴氰菊酯的总血浆清除率在口服和静脉途径中相同，均为0.11升/小时。单次口服给药后，溴氰菊酯迅速吸收，达峰时间为1.83小时。溴氰菊酯和4'-羟基溴氰菊酯的最大血浆浓度分别为0.46和0.26微克/毫升。4'-羟基溴氰菊酯的最大血浆浓度在3.29小时达到。发现溴氰菊酯的口服生物利用度为14.43%。溴氰菊酯及其代谢物4'-羟基溴氰菊酯的组织浓度-时间数据符合一室开放模型。在下丘脑、小脑、额叶皮质、尾状核、海马、延髓、输精管和尾骨肌组织中发现了相当浓度的溴氰菊酯和4'-羟基溴氰菊酯。小脑、额叶皮质、尾状核、延髓、输精管和尾骨肌组织中溴氰菊酯和4'-羟基溴氰菊酯的消除半衰期（t1/2el）（范围：溴氰菊酯为18 - 33小时，4'-羟基溴氰菊酯为15 - 28小时）比血浆中的（t1/2el分别为38.50和30.13小时）稍短。下丘脑和海马除外，其中溴氰菊酯的t1/2et分别为40.76和38.50小时。溴氰菊酯及其代谢物4'-羟基溴氰菊酯在神经组织中的蓄积通过组织/血浆浓度-时间曲线下面积（AUC）比值得到证实。溴氰菊酯的AUC组织/AUC血浆比值在延髓中为2.32，在下丘脑中为295.30，在其他组织中处于中间水平。
