Metabolism of aceclofenac to diclofenac in the domestic water buffalo Bubalus bubalis confirms it as a threat to Critically Endangered Gyps vultures in South Asia

• Published in: Environmental toxicology and pharmacology 2022-11, Vol.96, p.103984-103984, Article 103984
• Main Authors: Chandramohan, S., Mathesh, Karikalan, Mallord, John W., Naidoo, Vinny, Mahendran, K., Kesavan, Manickam, Gaur, Gyanendra K., Pawde, Abhijit M., Prakash, Nikita, Ranade, Sachin, Saikia, Debasish, Sharma, A.K., Shringarpure, Rohan, Green, Rhys E., Prakash, Vibhu M.
• Format: Article
• Language: English
• Subjects: Ecotoxicology; Liquid chromatography with mass spectrometry; Non-steroidal anti-inflammatory drugs; NSAID; Pharmacokinetics; Vulture declines
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2022.103984

Vulture declines in South Asia were caused by accidental poisoning by the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Although veterinary use of diclofenac has been banned, other vulture-toxic NSAIDs are legally available, including aceclofenac, which has been shown to metabolise into diclofenac in domestic cattle. We gave nine domestic water buffalo the recommended dose of aceclofenac (2 mg kg−1 body weight), collected blood at intervals up to 48 h, and carried out a pharmacokinetic analysis of aceclofenac and its metabolite diclofenac in plasma. Aceclofenac was rapidly converted to diclofenac, and was barely detectable in plasma at any sampling time. Diclofenac was present within 20 min, and peaked 4–8 h after dosing. Aceclofenac is a prodrug of diclofenac, and behaves similarly in domestic water buffalo as it did in domestic cattle, posing the same risk to vultures. We recommend an immediate ban on the veterinary use of aceclofenac across vulture-range countries. •Pharmacokinetic study of aceclofenac given to nine water buffaloes.•Aceclofenac barely detectable in buffalo plasma shortly after dosing.•Diclofenac measurable just 20 min after dosing with aceclofenac.•Diclofenac concentrations peaked at 4–8 h after dosing.•Aceclofenac is a prodrug of diclofenac, and will have the same effect on vultures.