title: Evaluation of the biliary and brain distribution of technetium Tc 99m sestamibi in healthy dogs with the ABCB1 wildtype genotype before and after treatment with spinosad.
abstract: OBJECTIVE
  To determine whether the reported drug-drug interaction between the flea medication spinosad and ivermectin is attributable to inhibition of P-glycoprotein by spinosad.
  
  
  METHODS
  6 healthy adult dogs with the ABCB1 wildtype genotype.
  
  
  METHODS
  The study was conducted as a prospective, masked, randomized crossover design. Six dogs were allocated to 2 groups; each dog served as its own control animal. Dogs in one of the groups received spinosad at the manufacturer's recommended dose; the other group received no treatment. Forty-eight hours later, scintigraphic imaging of the head and abdomen were performed with the radiolabeled P-glycoprotein substrate methoxy-isobutyl-isonitrile (sestamibi) in both groups of dogs. After a washout period of 60 days, the dogs in each group received the alternate treatment, and scintigraphic imaging again was performed 48 hours later. Gallbladder-to-liver and brain-to-neck musculature ratios of technetium Tc 99m sestamibi were calculated for each dog and compared between treatments.
  
  
  RESULTS
  No significant differences in gallbladder-to-liver or brain-to-neck musculature ratios were found between treatments.
  
  
  CONCLUSIONS
  Results provided evidence that spinosad did not inhibit P-glycoprotein function 48 hours after spinosad was administered at the manufacturer's recommended dose. Further investigations will be necessary to elucidate the mechanism of the reported toxic interaction between spinosad and ivermectin.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA. mackay.chris@gmail.com
authors.forename: Christopher S
authors.initials: CS
authors.lastname: MacKay
authors.forename: John S
authors.initials: JS
authors.lastname: Mattoon
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Roberts
authors.forename: Russell L
authors.initials: RL
authors.lastname: Tucker
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Morimoto
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Mealey
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001659:Biliary Tract / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D018592:Cross-Over Studies; D004285:Dogs / Q000235:genetics / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D007275:Injections, Intravenous; D018942:Macrolides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011446:Prospective Studies; D011877:Radionuclide Imaging / Q000662:veterinary; D017256:Technetium Tc 99m Sestamibi / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D004338:Drug Combinations; D018942:Macrolides; D017256:Technetium Tc 99m Sestamibi; C415329:spinosad