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.
