4.4 Article

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

Journal

JOURNAL OF VETERINARY INTERNAL MEDICINE
Volume 30, Issue 2, Pages 636-641

Publisher

WILEY-BLACKWELL
DOI: 10.1111/jvim.13827

Keywords

Collie; MDR1; P-glycoprotein

Funding

  1. CAS/CAHF Project Grant
  2. Post-graduate Research Fund
  3. McGeorge Research Fund

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BackgroundDog breeds with the ABCB1-1 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/ObjectivesThat ABCB1 mut/mut dogs have increased depth and duration of sedation after acepromazine IV compared to normal dogs (nor/nor). AnimalsTwenty-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. MethodsDogs 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. ResultsThe 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 ImportanceIn ABCB1 mut/mut dogs acepromazine dose rates should be reduced and careful monitoring performed during sedation.

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