TOXICOKINETICS OF DELTAMETHRIN AND ITS 4'-HO-METABOLITE IN THE RAT

The toxicokinetics of deltamethrin and its metabolite 4'-HO-deltamethr in 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 obtai ned after oral administration, Plasma, hypothalamus, cerebellum, front al cortex, caudate putamen, hippocampus, medulla oblongata, vas defere ns, and anococcygeus concentrations of deltamethrin and 4'-HO-deltamet hrin were determined by a high-performance liquid chromatographic assa y. The deltamethrin and 4'-HO-deltamethrin plasma profiles could be ad equately described by a two-compartment open model. For deltamethrin a nd 4'-HO-deltamethrin, the elimination half-lives (t 1/2(beta)) from p lasma 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-d(area)] and volume of distribution at steady state [ V-d(ss)] for deltamethrin were 5.33 and 2.04 liters, respectively, aft er iv administration, suggesting a considerable diffusion of the pyret hroid 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 sing le oral dose, deltamethrin was rapidly absorbed with a T-max of 1.83 h r. The maximum plasma concentrations of deltamethrin and 4'-HO-deltame thrin were 0.46 and 0.26 mu g/ml. The maximum plasma concentration of 4'-HO-deltamethrin was achieved at 3.29 hr. The oral bioavailability o f 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 d eltamethrin and 4'-HO-deltamethrin were found in the hypothalamus, cer ebellum, frontal cortex, caudate putamen, hippocampus, medulla oblonga ta, vas deferens, and anococcygeus tissues. The elimination half-lives (t 1/2(el)) for both deltamethrin and 4'-HO-deltamethrin were somewha t smaller for the cerebellum, frontal cortex, caudate putamen, medulla oblongata, vas deferens, and anococcygeus tissues (range, 18-33 hr fo r deltamethrin and 15-28 hr for 4'-HO-deltamethrin) than for plasma (t 1/2(el), 38.50 and 30.13 hr, respectively). Exceptions were seen for the hypothalamus and hippocampus in which the t 1/2(el)'s for deltamet hrin were 40.76 and 38.50 hr, respectively. Nervous tissue accumulatio n of deltamethrin and its metabolite 4'-HO-deltamethrin was evidenced by the tissue/plasma area under the concentration (AUG) versus time cu rve ratios. The ratios of AUC(tissue)/AUC(plasma) for deltamethrin wer e 2.32 in medulla oblongata, 295.30 in hypothalamus, and intermediate in other tissues. (C) 1996 Academic Press, Inc.