Pharmacokinetics of a novel endectoparasiticide topical formulation for cats, combining esafoxolaner, eprinomectin and praziquantel

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard((R)) Combo, a novel topical endectoparasiticide formulation for cats. The parasiticide potencies of topical esafoxolaner, eprinomectin and praziquantel, are based on transcutaneous absorption, systemic distribution, and exposure of respective target parasites. For each compound, the pharmacokinetic profile, non-interference, dose linearity/proportionality after one administration, and the accumulation and time to reach a steady state after repeated monthly administrations of the novel formulation, were investigated. After one topical application of NexGard((R)) Combo at the minimum recommended dose, the mean plasma concentration of esafoxolaner immediately reached (and remained at) a level supporting rapid onset and sustained efficacy against ectoparasites for at least 1 month. The mean C-max, T-max, T-1/2, and the topical bioavailability of esafoxolaner were 130 ng/mL, 7.1 days, 21.7 days and 47.2%, respectively, and the plasma profiles of eprinomectin and praziquantel supported their known endoparasiticide properties. No relevant interference between the three compounds was observed. Dose proportionality was demonstrated for the three compounds over a range of 0.5x to 2x the minimum recommended dose. Steady state after repeated monthly administrations was reached by the second dose for praziquantel and by the fifth dose for esafoxolaner and eprinomectin. Accumulation was limited and drug plasma concentrations were maintained within a safe level. L'esafoxolaner, un enantiomere purifie d'afoxolaner aux proprietes insecticides et acaricides, est combine a l'eprinomectine et au praziquantel dans NexGard((R)) Combo, une nouvelle formulation endectoparasiticide topique pour chats. Les pouvoirs parasiticides de l'esafoxolaner topique, de l'eprinomectine et du praziquantel sont bases sur l'absorption transcutanee, la distribution systemique et l'exposition des parasites cibles respectifs. Pour chaque compose, le profil pharmacocinetique, la non-interference, la linearite/proportionnalite de dose apres une administration, ainsi que l'accumulation et le temps necessaire pour atteindre un etat d'equilibre apres des administrations mensuelles repetees de la nouvelle formulation, ont ete etudies. Apres une application topique de NexGard((R)) Combo a la dose minimale recommandee, la concentration plasmatique moyenne d