Deshpande D, Hill K E, Mealey K L, Chambers J P, Gieseg M A
Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA.
J Vet Intern Med. 2016 Mar-Apr;30(2):636-41. doi: 10.1111/jvim.13827. Epub 2016 Jan 29.
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).
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.
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.
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).
In ABCB1 mut/mut dogs acepromazine dose rates should be reduced and careful monitoring performed during sedation.
携带ABCB1 - 1Δ突变的犬种具有大幅截短的无功能P - 糖蛋白。该突变纯合子犬（mut/mut）对伊维菌素、洛哌丁胺和长春新碱的毒性不良反应敏感。轶事报道表明，ABCB1 mut/mut犬使用乙酰丙嗪镇静时，深度和持续时间增加。
假设/目的：与正常犬（nor/nor）相比，ABCB1 mut/mut犬静脉注射乙酰丙嗪后镇静深度和持续时间增加。
29只粗毛柯利牧羊犬根据其ABCB1基因型分为3组犬：10只mut/mut、10只mut/nor和9只nor/nor。
给犬静脉注射0.04 mg/kg乙酰丙嗪。给药后6小时记录镇静水平、心率、呼吸频率和血压。计算并比较标准化镇静评分结果的曲线下面积（AUC）。
在所有时间点，ABCB1 mut/mut犬的镇静评分中位数均高于nor/nor犬，且mut/nor犬在最初2小时内更高。这些差异在任何单个时间点均无统计学意义（P > 0.05）。mut/mut犬的镇静评分中位数AUC显著高于nor/nor犬（P = 0.028），但mut/nor犬的AUC无显著差异（P = 0.45）。各组间心率、呼吸频率和血压无显著差异（P > 0.05）。
对于ABCB1 mut/mut犬，应降低乙酰丙嗪剂量率，并在镇静期间进行仔细监测。
