Possible emodepside toxicosis in a Collie with MDR1 gene mutation

• Autor(a) principal: Dias, Carlos André Ribeiro
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.26/16628
• topic: Collie; Emodepside; Adverse Drug Reactions; MDR 1 gene mutation; ABCB 1 gene; P Glycoprotein

The multi-drug resistance gene 1 (MDR1) is responsible for encoding an efflux transport protein designated P-glycoprotein (P-gp). The P-gp is expressed in various tissues such as the capillary endothelial cells of the brain, renal tubular cells, intestinal cells, skin, among others. It is also present in some types of neoplastic cells, where it is often overexpressed. It is a glycosylated transmembrane protein that transports several amphipathic and hydrophobic molecules, such as toxins and xenobiotics, including drugs commonly used in veterinary practice. A mutation in MDR1 gene is frequent in some dog breeds, and encodes the synthesis of a non-functional P-gp. The absence of P-gp in the blood-brain barrier may originate the accumulation of its substrates in the central nervous system, leading to neurotoxicity. Currently, a wide variety of molecules are known to be substrates of P-gp. This mutation has been classically associated with ivermectin neurotoxicity in dogs of Collie breeds. However, this mutation has been described in several other dog breeds, mainly herding breeds, and associated with toxicity of other drugs and toxins. This paper reports a clinical case of a strong suspicion of neurotoxicity associated with an overdose of emodepside in a Collie dog carrier of an homozygous mutation in the MDR1 gene. Although the neurotoxicity associated with the overdose of emodepside is recognized by the European Medicines Agency, this is, to our best knowledge, the first clinical report of a possible emodepside toxicosis. Considering the relevance of P-gp function in drug metabolism, it is of paramount importance to screen the MDR1 gene mutation, especially in dogs breeds where this mutation is frequent, so that safe drugs are used in the treatment of these animals