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

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.

Figure 1

Median dog sedation scores normalized to baseline (± the interquartile ranges), for the ABCB1‐1Δ genotypes mut/mut (solid line), mut/nor (short dashes), and nor/nor (long dashes) measured over 6 hours after IV administration of acepromazine.

Figure 2

Box and whisker plot of the sedation score AUCs for each genotype. The box shows the 1st and 3rd quartiles with the median plotted as the band inside the box. Whiskers show the upper and lower ranges with outliers plotted as circles.