7 Significance of species-specific metabolism in cats

The increase in reports of suspected cases of AC-poisoning to national veterinary and chemical authorities/institutes in Finland, Norway, and Sweden during 2018 and 2019 were almost all reports involving cats, despite other carnivores including dogs may also consume rodents. There are several likely explanations, e.g. cats are free ranging and rodent hunters whereas the dogs do not roam freely in the same way as cats. Cats may also be more efficient mice hunters compared to dogs, and generally the cats have smaller body size compared with dogs. The higher susceptibility to AC in cats compared to other carnivores may also be related to differences in drug metabolism (6), however, exact metabolic pathways of AC are not clear. To investigate the significance of this deficiency of AC detoxification in cats, a study was conducted by the Norwegian Veterinary Institute (NVI) where urine samples were analysed both freely and indirectly for conjugated AC by determining UGT conjugates after deconjugation with β-glucuronidase (total AC) (6). The analyses showed that there was little conjugated AC in cat urine, indicating that most cats lacked or had little ability to metabolise AC in the form of glucuronic acid conjugates.
In the study by Windahl et al. (1), the urine samples were screened for AC-metabolites. Significant amounts of AC were excreted unchanged in the urine, and some metabolites existed as different isomers. In total, four different isomers of sulphate phase II metabolites and one glucuronidated phase II metabolite were detected as well as one dechlorinated and two oxidated phase I metabolites. The detection of the glucuronic acid conjugate of AC indicates that glucuronidation of AC might be possible in cats, even though cats are known to have a limited capacity to form glucuronide metabolites of drugs. Accurate quantification of the metabolites could not be performed without authentic standards, which were not commercially available. Furthermore, it was questioned if the results might be influenced by rodent metabolism, if the cats were subjected to secondary poisoning. The authors call for further investigations of the relevance of various metabolites of the compound in relation to development of clinical disease and death in various animal species including cats (1).
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