Comparative pharmacokinetics of fluralaner in dogs and cats following single topical or intravenous administration

Background: Bravecto (TM) Chewable Tablets for Dogs, containing fluralaner as active ingredient, is an innovative treatment for flea and tick infestations that provides safe, rapid and long acting efficacy after a single oral administration in dogs. Topically applied fluralaner provides similar safe, rapid and long acting efficacy, both in dogs and in cats. The pharmacokinetic profile of fluralaner was evaluated in dogs and in cats following either topical or intravenous administration. Methods: Twenty four dogs and 24 cats received three different topical doses, with the mid-dose based on the respective minimum recommended dose, and one intravenous dose. Plasma samples were collected for 112 days and fluralaner concentrations were quantified using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic parameters were calculated using non-compartmental methods. Results: In dogs, fluralaner was readily absorbed from the topical administration site into the skin, subjacent tissues and blood. Fluralaner plasma concentrations showed an apparent plateau between similar to day 7 and 63, with individual t(max) seen within this time period. After the plasma plateau, concentrations declined slowly and were quantifiable for more than 12 weeks. In cats, fluralaner was readily systemically absorbed from the topical administration site, reaching maximum concentrations (C-max) in plasma between 3 and 21 days post administration, after which concentrations declined slowly, and were also quantifiable for more than 12 weeks. Systemic exposure, as shown by C-max and the area under the concentration versus time curve from time 0 to the last measurable concentration (AUC((0 -> t))) increased proportionally with dose in both species. Following intravenous administration fluralaner showed a relatively high apparent volume of distribution (V-z), a low plasma clearance (Cl), a long terminal half-life (t(1/2)) and a long mean residence time (MRT); thereby demonstrating a long persistence of fluralaner in both species. Conclusions: The pharmacokinetic characteristics of fluralaner explain its prolonged activity against fleas and ticks on both dogs and cats after a single topical administration.