P-glycoprotein (P-gp) is the product of the ABCB1 (formerly MDR1) gene. Dogs with the ABCB1-1Δ mutation are at increased risk for serious adverse reactions to P-gp substrate drugs. The goal of this study was to sequence the coding region of the gene in cats that experienced adverse reactions to P-gp substrate drugs (eg, macrocyclic lactones, loperamide, vinca alkaloids). Eight cats that had clinical signs of central nervous system (CNS) toxicosis after receiving ivermectin (n = 2), combination moxidectin and imidacloprid (n = 3), combination praziquantel and emodepside (n = 1), or selamectin (n = 2) at doses not expected to cause adverse reactions were tested. DNA was also collected from 1 cat treated with praziquantel-emodepside that did not develop CNS toxicity. DNA from 105 non-phenotyped cats was also obtained from a DNA bank.
The most significant finding was a nonsense (deletion) mutation in 1 of the ivermectin-treated cats. This cat was homozygous for the deletion mutation. The other cats were all homozygous for the wild-type allele. The nonsense mutation was identified in 4/105 nonphenotyped cats (1 homozygous and 3 heterozygous). The authors conclude that cats with the described nonsense mutation would be expected to show susceptibility to adverse effects of P-gp substrate drugs, similar to dogs with the ABCB1-1Δ mutation.
