Pharmacokinetic assessment of the dermal absorption of N,N-diethyl-m-toluamide (DEET) in cattle.

Model-independent pharmacokinetic methods based on statistical moments were applied to investigate the plasma disposition characteristics of N,N-diethyl-m-toluamide (DEET insect repellent) after single-dose treatment of experimental cattle by rapid intravenous injection (2.5-2.7 mg/kg) and by dermal application (10 mg/kg) to the back. DEET was determined in jugular blood samples by capillary GC with a nitrogen-selective detector and an internal standard of N,N-dipropyl-m-toluamide. Using weighted least squares linear regression analysis, the assay was validated over the concentration range of 19-1910 ng/ml of plasma. Comparison of areas under the plasma concentration-time curves after intravenous and dermal treatments of four Hereford heifers indicated that 72.9 +/- 8.3% (mean +/- SD) of the dermally applied dose was absorbed into the systemic circulation. The time-to-peak plasma concentrations following dermal treatments was 37.5 +/- 8.7 min. Apparent elimination rate constants were not significantly different between the two routes of administration. Linear pharmacokinetics was demonstrated with four additional cattle by comparing systemic clearance after intravenous infusion to steady-state plasma levels of approximately 0.5 and 2.5 micrograms/ml. The rapid and extensive dermal absorption of DEET observed in this study will probably contribute to a short duration of insect repellent action if ethanol-based sprays are used to protect cattle under field conditions.