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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

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  • 1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 2 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 3 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 4 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 5 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.
  • | 6 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164.

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.

Animals—6 healthy adult dogs with the ABCB1 wildtype genotype.

Procedures—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 and Clinical Relevance—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.

Contributor Notes

Supported by the Washington State University Graduate Student Research Grant and Morris Animal Foundation 2009 Pilot Study Award.

The authors thank Dr. John Gay for assistance with the statistical analysis and Sonja Fenimore for technical assistance.

Address correspondence to Dr. MacKay (mackay.chris@gmail.com).