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  • Title: Toxicokinetics of deltamethrin and its 4'-HO-metabolite in the rat.
    Author: Anadón A, Martinez-Larrañaga MR, Fernandez-Cruz ML, Diaz MJ, Fernandez MC, Martinez MA.
    Journal: Toxicol Appl Pharmacol; 1996 Nov; 141(1):8-16. PubMed ID: 8917670.
    Abstract:
    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.
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