title: Evaluation of the safety of spinosad and milbemycin 5-oxime orally administered to Collies with the MDR1 gene mutation.
abstract: 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.
  
  
  METHODS
  20 adult Collies homozygous or heterozygous for the MDR1 gene mutation that had signs of toxicosis after oral administration of ivermectin.
  
  
  METHODS
  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
  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.
authors.affiliation: Elanco Animal Health, Greenfield, IN 46140, USA. shermanjg@lilly.com
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Sherman
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Paul
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Firkins
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000009:adverse effects*; D004283:Dog Diseases / Q000139:chemically induced* / Q000235:genetics; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006579:Heterozygote; D006720:Homozygote; D018942:Macrolides / Q000008:administration & dosage / Q000009:adverse effects*; D009154:Mutation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000871:Anthelmintics; D004338:Drug Combinations; D018942:Macrolides; C078973:milbemycin oxime; C415329:spinosad