ABCG2 Polymorphisms and Predictive Fluoroquinolone Phototoxicity in Nondomestic Felids

Abstract

Fluoroquinolones are a widely used class of chemotherapeutics within veterinary medicine, prized for their broad-spectrum bactericidal activity. These drugs present a known risk of retinal phototoxicity in domestic cats (Felis catus); therefore, using lower doses and alternative antibiotic classes is encouraged in this species. This adverse drug effect of fluoroquinolones, and enrofloxacin specifically, has been determined to be species-specific in domestic felids. Four feline-specific missense variants in ABCG2 result in four amino acid changes (E159M, S279L, H283Q, and T644I) that are unique to the domestic cat compared with multiple other nonfeline mammalian species. These changes alter the ABCG2 protein involved with the cellular transmembrane transport of drugs, including fluoroquinolones, making the protein functionally defective in domestic cats. The predisposition to fluoroquinolone-mediated phototoxicity in nondomestic felids was explored in this study. At least eight nondomestic felids share the four ABCG2 missense variants with domestic cats, and eleven other felids shared at least three of the four domestic cat variants. Taken together, these results suggest the genetic potential for nondomestic felids to also experience fluoroquinolone-induced retinal phototoxicity; therefore, cautions similar to those for domestic cats should be followed for these drugs in the entire feline taxon.

Relevance of pharmacogenetics and pharmacogenomics in veterinary clinical practice: A review

“…This adverse drug reaction, particularly linked to enrofloxacin, has been identified as specific to the domestic felid species. In the domestic cat, four distinct missense variants in ABCG2 lead to four unique amino acid substitutions (E159M, S279L, H283Q, and T644I), distinguishing them from numerous other mammalian species (Gochenauer et al, 2022). Mealey and Burke (2015) found the genetic polymorphism that causes P-gp deficiency in cats.…”