Reduced Transdermal Absorption of N,N-Diethyl-m-toluamide from a New Topical Insect Repellent Formulation

Abstract

ABSTRACTExtensive absorption of the topical insect repellent N, N-diethyl-m-toluamide (DEET) causes systemic and local toxicities. This report describes the preparation and characterization of a new insect repellent formulation (FA), a PEG-polyacrylic acid polymer system, for its DEET release, in vitro skin permeation, and in vivo transdermal absorption properties; and for its relative repellency against Aedss aegypti mosquitoes. DEET release and skin permeation were studied in Franz diffusion cells. DEET transdermal absorption and relative repellency of FA were assessed in beagle dogs. A commercial DEET lotion (FB) and technical DEET (FC) were used as references. FA exhibited 19.5% and 61.7% decrease in DEET steady-state skin flux compared with FB and FC, respectively. At 15 mg DEET/kg, the absolute DEET transdermal bioavailability and Cmax were 13.4% and 154.3 ng/ml, respectively, for FA; and were 17.5% and 196.5 ng/ml, respectively, for FB. DEET half-lives (t1/2) for FA (2.52 hr) and FB (2.73 hr) were similar, while MRTfor FA (4.99 hr) was significantly greater (p < 0.05) than that for FB (4.38 hr). FA showed lower mosquito biting rates at 1, 2, 3, 4, 5, and 6 hr postdose at 0.5 mg DEET/cm2. FA exhibited reduced in vitro skin permeation and in vivo transdermal absorption of DEET as well as superior repellency compared with FB. The PEG-polyacrylic acid polymer system is of value in the formulation of DEET lotions.