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

2016; Wiley; Volume: 40; Issue: 1 Linguagem: Inglês

10.1111/jvp.12332

1365-2885

Laura Letendre, Jay Harriman, Marlene Drag, Amanda J. Mullins, Tadeusz Maliñski, Steffen Rehbein,

Helminth infection and control

The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NexGard Spectra® (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 (tmax ) was 2-4 h. The milbemycin tmax was 1-2 h. The terminal plasma half-life (t1/2 ) 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 (Vd ) 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.