OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabies patients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.
OBJECTIVE:Permethrin is an insecticide used in the treatment of lice and scabies infections. Although its efficacy and safety have been well documented, pharmacokinetic data are sparse. The objective of this study was to determine the systemic exposure of permethrin and the duration of residence in the human body following topical administration. METHODS: The study consisted of three parts. In six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg permethrin (cis/trans: 25/75) was administered to the hair of the head. In another six young healthy men (part 2) and in six male or female scabiespatients (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, and its conjugates was measured using a gas chromatography/electron capture detection method. RESULTS: Pharmacokinetics were similar in all study parts. The time of maximal urinary excretion rate was 12.3, 20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was well tolerated. CONCLUSIONS: The extent of systemic exposure following external therapeutic administration of permethrin is very low compared with doses used for preclinical toxicity studies, and elimination is virtually complete after 1 week. These data provide the pharmacokinetic basis for the clinical safety of topical permethrin.
Authors: Bruce A Buchholz; Ki Chang Ahn; Huazhang Huang; Shirley J Gee; Benjamin J Stewart; Ted J Ognibene; Bruce D Hammock Journal: Toxicol Sci Date: 2021-08-30 Impact factor: 4.109
Authors: Susan P Proctor; Matthew M Scarpaci; Alexis L Maule; Kristin J Heaton; Kathryn Taylor; Caitlin C Haven; Jennifer Rood; Maria Ospina; Antonia M Calafat Journal: Toxicol Lett Date: 2018-10-05 Impact factor: 4.372