Pharmacokinetics of spinosad and milbemycin oxime administered in combination and separately per os to dogs

Holmstrom, S. D., Totten, M. L., Newhall, K. B., Qiao, M., Riggs, K. L. Pharmacokinetics of spinosad and milbemycin oxime administered in combination and separately per os to dogs. J. vet. Pharmacol. Therap 35, 351-364. Pharmacokinetic (PK) studies were conducted to determine the potential PK interactions when spinosad and milbemycin oxime (MBO) are administered simultaneously. Investigations used commercial MBO tablets (C-MBO; Interceptor (R) Flavor Tabs, active ingredient MBO, Novartis Animal Health, Greensboro, NC, USA), novel-source (Elanco) MBO (E-MBO) in a gelatin capsule, spinosad API (Active Pharmaceutical Ingredient using registered manufacturing process) in a gelatin capsule, spinosad tablets (Comfortis (R) chewable beef flavored tablets, active ingredient spinosad, Elanco Animal Health, Greenfield, IN, USA), and the recently registered spinosad + E-MBO combination tablets (Trifexis (TM) chewable beef flavored tablets, active ingredients E-MBO and spinosad, Elanco Animal Health, Greenfield, IN, USA). Regardless of the source of MBO, in the presence of spinosad, greater systemic exposure of MBO was obtained as compared to MBO administered alone. Target animal safety studies conducted with dose multiples of spinosad and MBO indicate the increased exposure of MBO does not have implications on adverse clinical reactions. Further research is required to determine whether the higher levels of MBO have any implications for improved effectiveness as compared to C-MBO. Effectiveness studies conducted with 0.5 mg/kg of E-MBO in combination tablets demonstrated noninterference against C-MBO with both products achieving >99% effectiveness against the dose-limiting nematode, Ancylostoma caninum. No statistical differences were detected in the PK of MBO when comparing animals receiving E-MBO (without spinosad) and C-MBO. Also, the PK of spinosad was unaltered when co-administered with MBO.