Published as an abstract from the 22nd Annual Meeting of the North American Veterinary Dermatology Forum, Kauai, Hawaii, USA, April 2007. Veterinary Dermatology 2007; 18: 177.
The ABCB1-1Δ mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis
Article first published online: 18 DEC 2008
© 2008 The Authors. Journal compilation © 2008 ESVD and ACVD
Volume 20, Issue 1, pages 60–66, February 2009
How to Cite
Bissonnette, S., Paradis, M., Daneau, I. and Silversides, D. W. (2009), The ABCB1-1Δ mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis. Veterinary Dermatology, 20: 60–66. doi: 10.1111/j.1365-3164.2008.00731.x
Sources of Funding This study was funded by the Canadian Academy of Veterinary Dermatology.
Conflict of Interest No conflict of interest has been declared.
- Issue published online: 16 JAN 2009
- Article first published online: 18 DEC 2008
- Accepted 19 October 2008
P-glycoprotein (P-gp), encoded by the multiple drug resistance gene ABCB1 (also known as MDR1), is an integral component of the blood brain barrier crucial in limiting drug uptake into the central nervous system. Altered expression or function of P-gp, as seen in dogs of the collie lineage homozygous for the nt228(del4) mutation of the ABCB1 gene (ABCB1-1Δ), can result in potentially fatal neurotoxicosis, especially following administration of systemic macrocyclic lactones (SML). Occasionally, dogs from unrelated breeds develop subchronic signs of neurotoxicity when receiving SML to treat generalized demodicosis. It is possible that these dogs are heterozygous carriers of the ABCB1-1Δ mutation, resulting in decreased P-gp activity and central neurotoxicosis. Cheek swabs were collected from 28 dogs with generalized demodicosis that had shown subchronic signs of neurotoxicity following daily oral administration of ivermectin or other SML. Ten of these animals received concurrent systemic treatment with other confirmed or putative P-gp substrates. After DNA extraction, the relevant portion of the ABCB1 gene was amplified by polymerase chain reaction, and sequenced. Twenty-seven dogs were homozygous normal while one dog was heterozygous for the ABCB1-1Δ mutation. Therefore, with the exception of one dog, the observed neurotoxicity could not be attributed to the ABCB1-1Δ mutation. Possible explanations for the adverse reactions observed include pharmacological interactions (administration of SML with other P-gp substrates or inhibitors), excessively high doses, polymorphisms in P-gp expression, uncharacterized mutations in the ABCB1 gene or in another gene, or phenomena unrelated to the SML–P-gp interaction.