College of Veterinary Medicine

Veterinary Clinical Pharmacology Lab 

Current Research & Publications


Research into the breeds that are affected and which drugs cause problems for dogs that have the MDR1 mutation is still in progress at the Washington State University College of Veterinary Medicine. We are looking at other breeds to see if they have the mutation and taking reports by owners and veterinarians on other drugs that may cause problems for these dogs.

We are currently seeking samples from dogs of the herding breeds (Collies, Australian Shepherds, etc.) that have experienced unexpected reactions to drugs when administered at normal doses.

We are also working with veterinarians in Australia and France to determine the frequency of the mutation in herding breeds in those countries. Results of these tests are expected this year.

We are looking ahead to three important research directions

  • We'd like to expand our research to identify other dog breeds that experience a high incidence of adverse drug reactions.
  • We believe there may be other chemicals and drugs that may cause problems through this system or similar gene mutations. We'd like to further define which chemicals and drugs those are.
  • A key problem with getting needed drugs into the brain and keeping them there is the very system that we discovered through our study of the MDR1 gene mutation. Could this gene or others be exploited when needed to ensure that we can get vital chemotherapeutic drugs into the brain and hold them there? Further studies by our research group may answer that question and provide a less toxic, more effective way to treat cancers or diseases of the brain.

More Information and Publications

More about the initial discovery of the cause of ivermectin sensitivity.

Researcher explains Collies' deadly reaction to medication. Dog Fancy, June 2002, p24.

Mutant-gene discovery could help save Collies. Dog World, May 2002, p13.

Scientific and Technical Publications (by year)


2008-2009

Barbet J, Snook T, Gay JM, Mealey KL ABCB1 (MDR1) genotype is associated with adverse reactions in dogs treated with milbemycin oxime for generalized demodicosis; Vet Dermatol 2009; 20;111-114.

Martinez M, Modric S, Sharkey M, Troutman L, Walker L, Mealey K. The pharmacogenomics of P-glycoprotein and its role in veterinary medicine. J Vet Pharm Ther 2008; 31:285-300.

Mealey KL Canine ABCB1 and Macrocyclic Lactones: Heartworm Prevention and Pharmacogenetics. Vet Parasit 2008;158(3):215-222.

Mealey KL, Fidel J, Gay JM, Impellizeri J, Clifford C, Bergman PJ. ABCB1-1D Polymorphism can predict hematologic toxicity in dogs treated with vincristine; J Vet Int Med 2008;996-1000.

Mealey KL, Meurs KM. Breed Distribution and Frequency of the ABCB1-1D (Multidrug Sensitivity) Polymorphism in Dogs; J Am Vet Med Assoc, 2008;233:921-924.

Mealey KL, Greene S, Bagley R, Gay J, Tucker R, Gavin P, Waiting D, Schmidt K, Nelson F. P-glycoprotein contributes to the blood-brain, but not blood-CSF, barrier in a spontaneous canine P-glycoprotein knockout model Drug Metab Disp, 2008;36(6):1073-1079.

2006-2007

Chadwick L.West; Katrina L. Mealey Assessment of antiepileptic drugs as substrates for canine P-glycoprotein. Am J Vet Res 2007 10:1106-1110.

Henick RA, Kellum HB, Bentjen SA, Mealey KL. Digoxin and mexiletine sensitivity in a collie with the mdr1 mutation. J Vet Int Med 2006;20:415-417.

Mealey KL. Adverse Drug Reactions in Herding Breeds. Compendium of Continuing Education for the Practicing Veterinarian 2006;28:23-33.

Mealey KL. Pharmacogenetics in Veterinary Medicine. Veterinary Clinics of North America: Small Animal Practice 2006;36:961-973.

Mealey KL, Gay JM, Martin LG, Waiting DK. Comparison of the hypothalamic-pituitary-adrenal axis in MDR1-1D and MDR1 wildtype dogs. J Vet Emergency Crit Care 2007;17:61-66.

2004-2005

Hugnet C, Bentjen SA, Mealey KL. Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of Collies from France. Journal of Veterinary Pharmacology and Therapeutics, 2004;27:227-229.

Kukanich B, Lascelles BD, Aman AM, Mealey KL, Papich MG. The effects of inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid secretion on the oral bioavailability of methadone in dogs. 2005;28:461-466
Mealey KL. Therapeutic implications of the MDR1 gene. Journal of Veterinary Pharmacology and Therapeutics, 2004;27:257-264.

Mealey KL, Munyard KA, Bentjen SA. Frequency of the MDR1 mutation associated with multidrug sensitivity in a sample of herding breed dogs living in Australia. Veterinary Parasitology, 2005;131:193-196.

Neff MW, Robertson KR, Wong A, Safra N, Broman KW, Slatkin M, Mealey KL, Pedersen NC. Breed distribution and history of canine mdr1-1d, a pharmacogenetic mutation that marks the emergence of breeds of the collie lineage. Proceedings of the National Academy of Sciences, 2004; 101:11725-11730.

Sartor LL, Bentjen SA, Trepanier L, Mealey KL. Loperamide toxicity after therapeutic doses in a Collie with the MDR1 mutation associated with ivermectin sensitivity. Journal of Veterinary Internal Medicine, 2004;18:117-118.

2001-2003

Mealey KL, Northrop NC, Bentjen SA. Increased susceptibility to P-glycoprotein substrate chemotherapeutic agents in a Collie with the MDR1 deletion mutation associated with ivermectin sensitivity, Journal of the American Veterinary Medical Association, 2003;223:1453-1455.

Mealey KL, Bentjen SA. Sequence and structural analysis of the downstream promoter of the canine mdr1 gene, Journal of Veterinary and Comparative Oncology, 2003;1(1):30-35.

Mealey KL, Bentjen SA, Waiting D. Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of Collies from the northwestern United States. American Journal of Veterinary Research, 2002;63:479-481.

Mealey KL, Bentjen SA, Gay J, Cantor GH. Ivermectin sensitivity in Collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics, 2001;11:727-733.Nelson OL, Carsten E, Bentjen SA, Mealey, KL. Ivermectin toxicity in an Australian Shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in Collies, Journal of Veterinary Internal Medicine, 2003;17:354-356.
Last Edited: Jul 17, 2009 3:54 PM   

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