Inherent P-glycoprotein deficiency and macrocyclic lactone toxicity in an Australian Maine Coon cat homozygous for ABCB1 1930_1931del TC

Case summary A 9-month-old castrated male Maine Coon cat developed tongue protrusion, mydriasis, generalised weakness and ataxia after routine application, as per label guidelines, of NexGard Spectra (Boehringer Ingelheim; active ingredients praziquantel 83 g/l, esafoxolaner 12 g/l, eprinomectin 4 g/l). The cat was managed conservatively for suspected macrocyclic lactone toxicity and made a complete recovery over 3 months. Further testing identified the cat was homozygous for ABCB1 1930_1931del TC, a recently identified variant for encoding for the drug transporter molecule P-glycoprotein (P-gp). Cats who are homozygous for ABCB1 1930_1931del TC have a non-functional P-gp. Because of this change, affected cats have an increased risk of neurotoxicity of macrocyclic lactone and other P-gp substrate drugs, as seen in this case. Relevance and novel information This is the first documented case of a cat homozygous for ABCB1 1930_1931del TC in Australia with macrocyclic lactone toxicity after administration of an eprinomectin-containing product at label doses. Further awareness of this genetic variant and implications in use of substrate drugs, including new generation macrocyclic lactones, are required to improve the safety of these products in the general cat population. This includes the development and promotion of commercially available screening tests to facilitate personalised treatment advice.