The intravenous and oral pharmacokinetics of afoxolaner and milbemycin oxime when used as a combination chewable parasiticide for dogs

The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NEXGARD SPECTRA((R)) (Merial), a fixed combination chewable formulation of these two active pharmaceutical ingredients. Absorption of actives was rapid at levels that provide the minimum effective doses of 2.5 mg/kg and 0.5 mg/kg of afoxolaner and milbemycin oxime, respectively. The time to maximum afoxolaner plasma concentrations (t(max)) was 2- 4 h. The milbemycin tmax was 1-2 h. The terminal plasma half-life (t(1/2)) and the oral bioavailability were 14 +/- 3 days and 88.3% for afoxolaner, 1.6 +/- 0.4 days and 80.5% for milbemycin oxime A3 and 3.3 +/- 1.4 days and 65.1% for milbemycin oxime A4. The volume of distribution (V-d) and systemic clearance (Cls) were determined following an IV dose of afoxolaner or milbemycin oxime. The Vd was 2.6 +/- 0.6, 2.7 +/- 0.4 and 2.6 +/- 0.6 L/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The Cls was 5.0 +/- 1.2, 75 +/- 22 and 41 +/- 12 mL/h/kg for afoxolaner, milbemycin oxime A3 and milbemycin oxime A4, respectively. The pharmacokinetic profile for the combination of afoxolaner and milbemycin oxime supports the rapid onset and a sustained efficacy for afoxolaner against ectoparasites and the known endoparasitic activity of milbemycin oxime.