title: ABCB1-1 Delta (MDR1-1 Delta) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis.
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.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Joy L
authors.initials: JL
authors.lastname: Barbet
authors.forename: Tara
authors.initials: T
authors.lastname: Snook
authors.forename: John M
authors.initials: JM
authors.lastname: Gay
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Mealey
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000009:adverse effects* / Q000627:therapeutic use; D001259:Ataxia / Q000139:chemically induced / Q000235:genetics / Q000662:veterinary; D003881:Dermatomycoses / Q000188:drug therapy / Q000662:veterinary*; D004283:Dog Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018942:Macrolides / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000871:Anthelmintics; D018942:Macrolides; C078973:milbemycin oxime