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

Vet Dermatol. 2009 Apr;20(2):111-4. doi: 10.1111/j.1365-3164.2008.00725.x. Epub 2008 Dec 18.

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 ABCB1-1 Delta 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 ABCB1-1 Delta mutation developed ataxia. Assessing the ABCB1-1 Delta genotype prior to MO administration may prevent neurological toxicity in these patients.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Anthelmintics / adverse effects*
  • Anthelmintics / therapeutic use
  • Ataxia / chemically induced
  • Ataxia / genetics
  • Ataxia / veterinary
  • Dermatomycoses / drug therapy
  • Dermatomycoses / veterinary*
  • Dog Diseases / chemically induced
  • Dog Diseases / drug therapy
  • Dog Diseases / genetics
  • Dogs
  • Female
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genotype
  • Macrolides / adverse effects*
  • Macrolides / therapeutic use
  • Male

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anthelmintics
  • Macrolides
  • milbemycin oxime