title: 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.
  
  
  OBJECTIVE
  That ABCB1 mut/mut dogs have increased depth and duration of sedation after acepromazine IV compared to normal dogs (nor/nor).
  
  
  METHODS
  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
  In ABCB1 mut/mut dogs acepromazine dose rates should be reduced and careful monitoring performed during sedation.
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: Deshpande
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: K E
authors.identifier: http://orcid.org/0000-0003-1549-8828
authors.initials: KE
authors.lastname: Hill
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA.
authors.forename: K L
authors.initials: KL
authors.lastname: Mealey
authors.affiliation: Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: J P
authors.initials: JP
authors.lastname: Chambers
authors.affiliation: Veterinary Health Research, Waikato Innovation Park, Hamilton, New Zealand.
authors.forename: M A
authors.initials: MA
authors.lastname: Gieseg
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000075:Acepromazine / Q000008:administration & dosage / Q000494:pharmacology*; D061605:Administration, Intravenous; D000818:Animals; D019540:Area Under Curve; D016292:Procedural Sedation / Q000662:veterinary*; D004285:Dogs / Q000235:genetics*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D009154:Mutation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018492:Dopamine Antagonists; D000075:Acepromazine
keywords: Collie; MDR1; P-glycoprotein
references.citation: Eur J Pharmacol. 2003 Jan 24;460(2-3):85-91
references.pmid: 12559367
references.citation: J Clin Invest. 1996 Jun 1;97(11):2517-24
references.pmid: 8647944
references.citation: Drug Metab Dispos. 1981 Jan-Feb;9(1):30-6
references.pmid: 6111428
references.citation: J Vet Intern Med. 2006 Mar-Apr;20(2):415-7
references.pmid: 16594604
references.citation: Drug Metab Dispos. 2008 Jun;36(6):1073-9
references.pmid: 18332085
references.citation: J Vet Intern Med. 2003 May-Jun;17(3):354-6
references.pmid: 12774979
references.citation: J Small Anim Pract. 2007 Feb;48(2):76-9
references.pmid: 17286659
references.citation: Anesthesiology. 2000 May;92(5):1392-9
references.pmid: 10781286
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11725-30
references.pmid: 15289602
references.citation: J Vet Intern Med. 2004 Jan-Feb;18(1):117-8
references.pmid: 14765742
references.citation: J Am Vet Med Assoc. 2003 Nov 15;223(10):1453-5, 1434
references.pmid: 14627096
references.citation: J Am Vet Med Assoc. 2010 Nov 15;237(10):1155-9
references.pmid: 21073386
references.citation: Anesthesiology. 2002 Apr;96(4):913-20
references.pmid: 11964599
references.citation: J Am Vet Med Assoc. 2014 May 1;244(9):1075-80
references.pmid: 24739118
references.citation: J Am Vet Med Assoc. 2005 Apr 1;226(7):1092-4
references.pmid: 15825733
references.citation: J Vet Pharmacol Ther. 2008 Aug;31(4):285-300
references.pmid: 18638289
references.citation: J Am Vet Med Assoc. 2001 Apr 1;218(7):1101-5
references.pmid: 11318359
references.citation: Pharmacogenetics. 2001 Nov;11(8):727-33
references.pmid: 11692082
references.citation: J Small Anim Pract. 2012 Mar;53(3):185-7
references.pmid: 22122243
references.citation: Physiol Rev. 2006 Oct;86(4):1179-236
references.pmid: 17015488
references.citation: Vet Parasitol. 2008 Dec 10;158(3):215-22
references.pmid: 18922637
references.citation: J Biol Chem. 1993 Jul 25;268(21):16059-64
references.pmid: 8101846
references.citation: J Vet Intern Med. 2008 Jul-Aug;22(4):996-1000
references.pmid: 18537875