Metabolism of aceclofenac in cattle to vulture-killing diclofenac

Abstract

The non-steroidal anti-inflammatory drug (NSAID) diclofenac is highly toxic to Gyps vultures and its recent widespread use in South Asia caused catastrophic declines in at least three scavenging raptors. The manufacture of veterinary formulations of diclofenac has since been banned across the region with mixed success. However, at least 12 other NSAIDs are available for veterinary use in South Asia. Aceclofenac is one of these compounds and it is known to metabolise into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. In this study, we give six cattle the recommended dose of aceclofenac (2 mg/kg), collect blood along a time series and undertake a pharmacokinetic analysis of aceclofenac and diclofenac-metabolites in their plasma using liquid chromatography with mass spectrometry. We found that nearly all of the aceclofenac administered to the cattle was very rapidly metabolised into diclofenac. Therefore, treating livestock with pure diclofenac or aceclofenac poses the same risk to vultures. This fact, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, fortifies the need for an immediate ban on all aceclofenac formulations that can be used to treat livestock. Without such a ban, the recovery of vultures across South Asia will not be successful.