PHARMACOKINETICS OF INSECT REPELLENT N,N-DIETHYL-M-TOLUAMIDE IN BEAGLE DOGS FOLLOWING INTRAVENOUS AND TOPICAL ROUTES OF ADMINISTRATION

The common topical insect repellent N,N-diethyl-m-toluamide (DEET) has caused serious adverse effects in the users of DEET products due to i ts high skin permeability. This study investigated the pharmacokinetic s of DEET following iv and dermal routes of administration in beagle d ogs. The pharmacokinetics of DEET was linear over the dose range of 2. 5-6.0 mg/kg. Following the iv dosing, plasma DEET concentrations decli ned biexponentially with an elimination half-life of 2.56 h. Volume of distribution at steady-state, systematic clearance, and mean residenc e time were estimated as 6.21 L/kg, 2.66 L/h/kg, and 2.34 h, respectiv ely, indicating that DEET underwent extensive extravascular distributi on and rapid elimination. After the dermal application of a commercial lotion and a new DEET lotion at 15 mg of DEET/kg, plasma DEFT concent rations 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 lot ion. The difference in DEFT transdermal absorption between the two lot ions suggested that commercial DEET products could be optimized for re duced DEET absorption for safer use.