The Effect of the Canine ABCB1-1Δ Mutation on Sedation after Intravenous Administration of Acepromazine

J Vet Intern Med. Mar-Apr 2016;30(2):636-41. doi: 10.1111/jvim.13827. Epub 2016 Jan 29.

Abstract

Background: Dog breeds with the ABCB1-1Δ mutation have substantially truncated nonfunctional P-glycoprotein. Dogs homozygous for this mutation (mut/mut) are susceptible to the toxic adverse effects of ivermectin, loperamide, and vincristine. Anecdotal reports suggested ABCB1 mut/mut dogs showed increased depth and duration of acepromazine sedation.

Hypothesis/objectives: That ABCB1 mut/mut dogs have increased depth and duration of sedation after acepromazine IV compared to normal dogs (nor/nor).

Animals: Twenty-nine rough-coated collies were divided into 3 groups of dogs based on their ABCB1 genotype: 10 mut/mut, 10 mut/nor, and 9 nor/nor.

Methods: Dogs were given 0.04 mg/kg of acepromazine IV. Level of sedation, heart rate, respiratory rate, and blood pressure were recorded for 6 hours after acepromazine administration. Area under the curves (AUCs) of the normalized sedation score results were calculated and compared.

Results: The median sedation scores for ABCB1 mut/mut dogs were higher than nor/nor dogs at all time points and were higher in mut/nor dogs for the first 2 hours. These differences were not found to be significant for any individual time point (P > .05). The median sedation score AUC for mut/mut dogs was significantly higher than nor/nor dogs (P = .028), but the AUC for mut/nor dogs was not (P = .45). There were no significant differences between groups for heart rate, respiratory rate, and blood pressure (P > .05).

Conclusions and clinical importance: In ABCB1 mut/mut dogs acepromazine dose rates should be reduced and careful monitoring performed during sedation.

Keywords: Collie; MDR1; P-glycoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Acepromazine / administration & dosage
  • Acepromazine / pharmacology*
  • Administration, Intravenous
  • Animals
  • Area Under Curve
  • Conscious Sedation / veterinary*
  • Dogs / genetics*
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Genotype
  • Mutation

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Dopamine Antagonists
  • Acepromazine