Evaluation of the safety of spinosad and milbemycin 5-oxime orally administered to Collies with the MDR1 gene mutation

Objective - To determine whether signs of avermectin (AVM)-milbemycin (MB) toxicosis would be evident in AVM-MB-sensitive Collies after treatment with an experimental formulation of spinosad alone or spinosad combined with MB 5-oxime (MBO) at doses up to 5 and 10 times the MBO maximum label dose. Animals - 20 adult Collies homozygous or heterozygous for the MDR1 gene mutation that had signs of toxicosis after oral administration of ivermectin. Procedures - On the basis of AVM-MB sensitivity score, each dog was assigned in a randomized block design to 1 of 5 treatment groups (control group, 300 mg of spinosad/kg [5 times maximum label dose], 180 mg of spinosad/kg with 3 mg of MBO/kg [3 times maximum MBO label dose], 300 mg of spinosad/kg with 5 mg of MBO/kg, and 300 mg of spinosad/kg with 10 mg of MBO/kg). Treatments were administered orally as a sequence of single doses during 5 consecutive days. After a 28-day washout period, treatment sequences were repeated. Posttreatment observation and scoring by blinded observers were conducted to specifically include neurologic abnormalities typical of AVM-MB toxicosis, such as signs of depression, ataxia, mydriasis, and hypersalivation. Results - No signs of AVM-MB toxicosis were attributed to treatment in any dog during the study. Conclusions and Clinical Relevance - Results indicated that oral administration of spinosad at 300 mg/kg alone or in combination with MBO at doses up to 10 mg/kg did not cause signs of AVM-MB toxicosis in AVM-MB-sensitive dogs with the MDR1 gene mutation.