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

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.

Toxic Interactions of Prophylactic Drugs and Pesticides

“…DEET underwent metabolic transformation mediated by esterases and cytochrome p450 enzymes, resulted in formation of metabolites of w-toluic acid and m-toluamide. This is in agreement with previous reports following dermal dose of DEET in rats and dogs Qiu et al, 1997), and in accordance with previous studies reported that DEET metabolism mediated by iV-dealkylation, ring hydroxylation and ring dealkylation following in vitro incubation with rat liver microsomes (Constantino and Iley, 1999;Taylor, 1986). These findings are also consistent with our recent results obtained following in vivo and in vitro incubation of DEET with human liver microsomes (Abu-Qare and Abou- Donia, 2001b;2001d).…”

“…It seems that dose, and route of administration of DEET were factors in the determination of its pharmacokinetic profile and its rate and pattern of elimination. Qiu et al (1997) reported that the pharmacokinetic profile of DEET was bei-exponential with an elimination half-life of 2.7 h, after dermal dose in Beagle dogs, where its plasma concentration peaked 1-2 h after dosing. Furthermore reported that blood serum concentration of DEET was 12347 ng/ml following an i.p injection of 500 mg/kg in male rats.…”

Current sunscreen issues: 2007 Food and Drug Administration sunscreen labelling recommendations and combination sunscreen/insect repellent products

“…26 Designed as topical agents, repellents and sunscreens under ideal application conditions should exert minimal transdermal and systemic absorption. Animal 27,28 and human 29 studies have indicated that when individually applied, DEET is capable of transdermal and systemic absorption. Furthermore, studies with human volunteers have indicated that oxybenzone is also capable of transdermal and systemic absorption.…”

Simultaneous analysis of insect repellent DEET, sunscreen oxybenzone and five relevant metabolites by reversed-phase HPLC with UV detection: Application to an in vivo study in a piglet model

“…1b) is an essential UVA/UVB blocking agent that is extensively used in commercially available sunscreen products [3,4]. Systemic absorption of both compounds after topical applications has been separately studied [5][6][7]. Recently we reported a synergistic percutaneous permeation between DEET and oxybenzone after the two active ingredients were used simultaneously in vitro [8,9].…”