Pharmacokinetics of Insect Repellent N,N-Diethyl-m-toluamide in Beagle Dogs following Intravenous and Topical Routes of Administration

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Abstract
The common topical insect repellent N,N-diethyl-m-toluamide (DEET) has caused serious adverse effects in the users of DEET products due to its high skin permeability. This study investigated the pharmacokinetics of DEET following i.v. and dermal routes of administration in beagle dogs. The pharmacokinetics of DEET was linear over the dose range of 2.5-6.0 mg/kg. Following the i.v. dosing, plasma DEET concentrations declined biexponentially with an elimination half-life of 2.56 h. Volume of distribution at steady-state, systematic clearance, and mean residence time were estimated as 6.21 L/kg, 2.66 L/h/kg, and 2.34 h, respectively, indicating that DEET underwent extensive extravascular distribution and rapid elimination. After the dermal application of a commercial lotion and a new DEET lotion at 15 mg of DEET/kg, plasma DEET concentrations peaked at 1-2 h postdose. The DEET transdermal bioavailability and mean absorption time were 18.3% and 2.05 h, respectively, for the commercial lotion and 14.0% and 2.66 h, respectively, for the new lotion. The difference in DEET transdermal absorption between the two lotions suggested that commercial DEET products could be optimized for reduced DEET absorption for safer use.

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