title: Metabolism of aceclofenac in cattle to vulture-killing diclofenac.
abstract: The nonsteroidal 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 3 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 metabolize into diclofenac in some mammal species. The metabolic pathway of aceclofenac in cattle, the primary food of vultures in South Asia, is unknown. We gave 6 cattle the recommended dose of aceclofenac (2 mg/kg), collected blood thereafter at intervals for up to 12 h, and used liquid chromatography with mass spectrometry in a pharmacokinetic analysis of aceclofenac and diclofenac in the plasma. Nearly all the aceclofenac administered to the cattle was very rapidly metabolized into diclofenac. At 2 h, half the aceclofenac had been converted into diclofenac, and at 12 h four-fifths of the aceclofenac had been converted into diclofenac. Therefore, administering aceclofenac to livestock poses the same risk to vultures as administering diclofenac to livestock. This, coupled with the risk that aceclofenac may replace diclofenac in the veterinary market, points to 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.
authors.affiliation: RSPB Centre for Conservation Science, The Lodge, Sandy, Bedfordshire, SG19 2DL, U.K.. toby.galligan@rspb.org.uk.
authors.forename: T H
authors.initials: TH
authors.lastname: Galligan
authors.affiliation: Environmental Research Institute, University of the Highlands and Islands, Castle Street, Thurso, Scotland, KW14 7JD, U.K.
authors.forename: M A
authors.initials: MA
authors.lastname: Taggart
authors.affiliation: RSPB Centre for Conservation Science, The Lodge, Sandy, Bedfordshire, SG19 2DL, U.K.|Wildlife Conservation Society, P.O. Box 277, Goroka, Eastern Highlands Province 441, Papua New Guinea.
authors.forename: R J
authors.initials: RJ
authors.lastname: Cuthbert
authors.affiliation: Environmental Research Institute, University of the Highlands and Islands, Castle Street, Thurso, Scotland, KW14 7JD, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Svobodova
authors.affiliation: Biomedical Research Centre, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Gauteng, 0110, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Chipangura
authors.affiliation: SAC Consulting Veterinary Services, Janetstown, Thurso, Scotland, KW14 7XF, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Alderson
authors.affiliation: Bombay Natural History Society, Hornbill House, Mumbai, 400023, India.
authors.forename: V M
authors.initials: VM
authors.lastname: Prakash
authors.affiliation: Wildlife Conservation Society, P.O. Box 277, Goroka, Eastern Highlands Province 441, Papua New Guinea.
authors.forename: V
authors.initials: V
authors.lastname: Naidoo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001208:Asia; D002417:Cattle; D003247:Conservation of Natural Resources; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D056727:Endangered Species; D046093:Falconiformes
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; C056498:aceclofenac
keywords: Gyps; NSAID; amenazas a los buitres; declinación de buitres; drogas anti-inflamatorias no-esteroidales; ecotoxicology; ecotoxicología; farmacocinética; farmacéuticos en el ambiente; nonsteroidal anti-inflammatory drugs; pharmaceuticals in the environment; pharmacokinetics; threats to vultures; vulture declines