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®(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 tmaxwas 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 Vdwas 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.
Merial, Inc., Duluth, GA, USA.
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Letendre
Merial, Inc., Duluth, GA, USA.
J
J
Harriman
Merial, Inc., Duluth, GA, USA.
M
M
Drag
Merial, Inc., Duluth, GA, USA.
A
A
Mullins
Merial, Inc., Duluth, GA, USA.
T
T
Malinski
Merial, Inc., Duluth, GA, USA.
S
S
Rehbein
D056810:Acaricides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061605:Administration, Intravenous / Q000662:veterinary; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004283:Dog Diseases / Q000188:drug therapy* / Q000469:parasitology; D004285:Dogs; D004338:Drug Combinations; D005260:Female; D058267:Flea Infestations / Q000188:drug therapy / Q000662:veterinary*; D007306:Insecticides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007555:Isoxazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018942:Macrolides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013984:Tick Infestations / Q000188:drug therapy / Q000662:veterinary*
D056810:Acaricides; D004338:Drug Combinations; D007306:Insecticides; D007555:Isoxazoles; D018942:Macrolides; D009281:Naphthalenes; C000589002:afoxolaner; C078973:milbemycin oxime