ABCB1-1Δ (MDR1-1Δ) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis

Authors

  • Joy L. Barbet,

    1. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
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  • Tara Snook,

    1. Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA
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    • Present address: Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.

  • John M. Gay,

    1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
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  • Katrina L. Mealey

    1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA
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  • Sources of Funding
    This study is self-funded.
    Conflict of Interest
    Washington State University owns the patent for the ABCB1 genotyping technology reported in this manuscript. The Veterinary Clinical Pharmacology Laboratory licenses this technology from Washington State University through a Service Center Agreement. As the inventor of the ABCB1 genotyping technology, it is possible that one of the authors (K Mealey) will directly receive royalty distributions if all patent costs, administration costs and other fees (i.e. payment of royalties to Roche Molecular Systems, Inc) are paid in full.
    J.L. Barbet and Tara Snook share first authorship of this paper.

K.L. Mealey, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610, USA. E-mail: kmealey@vetmed.wsu.edu

Abstract

Twenty-two dogs diagnosed with generalized demodicosis were treated with milbemycin oxime (MO) because of poor response to previous therapies or because the dog was a breed known to be susceptible to ivermectin toxicosis. Fifteen of the 22 dogs were herding breeds. Doses of MO ranged from 1.0 to 2.2 mg kg−1 day−1 per os. Cheek swab samples were obtained in order to determine each dog's ABCB1 genotype. Adverse drug reactions were recorded for each dog by the owners and/or veterinarians. The ABCB1-1Δ genotype was significantly associated with the development of an adverse reaction (neurological toxicity) after treatment with MO. None of the 19 dogs with the wild-type ABCB1 allele experienced adverse reactions, whereas two dogs homozygous for the ABCB1-1Δ mutation developed ataxia. Assessing the ABCB1-1Δ genotype prior to MO administration may prevent neurological toxicity in these patients.

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