The intravenous and oral pharmacokinetics of afoxolaner and milbemycin oxime when used as a combination chewable parasiticide for dogs. Issue 1 (7th September 2016)

• Record Type: Journal Article
• Authors: Letendre, L.; Harriman, J.; Drag, M.; Mullins, A.; Malinski, T.; Rehbein, S.
• Is Part Of: Journal of veterinary pharmacology and therapeutics. Volume 40:Issue 1(2017)
• Page Start: 35
• Page End: 43
• Publication Date: 2016-09-07
• Subjects: Veterinary pharmacology -- Periodicals; Therapeutics -- Periodicals; 636.0895105
• DOI: 10.1111/jvp.12332
• Languages: English
• ISSNs: 0140-7783

Abstract

Abstract : The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration ofNexGard 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 ( t max ) was 2–4 h. The milbemycin t max 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 (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.