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