Toxicity of non-steroidal anti-inflammatory drugs to Gyps vultures: a new threat from ketoprofen

Abstract

Three Gyps vulture species are on the brink of extinction in South Asia owing to the veterinary non-steroidal anti-inflammatory drug (NSAID) diclofenac. Carcasses of domesticated ungulates are the main food source for Asia's vultures and birds die from kidney failure after consuming diclofenac-contaminated tissues. Here, we report on the safety testing of the NSAID ketoprofen, which was not reported to cause mortality in clinical treatment of scavenging birds and is rapidly eliminated from livestock tissues. Safety testing was undertaken using captive non-releasable Cape griffon vultures ( Gyps coprotheres ) and wild-caught African white-backed vultures ( G. africanus ), both previously identified as susceptible to diclofenac and suitable surrogates. Ketoprofen doses ranged from 0.5 to 5 mg kg −1 vulture body weight, based upon recommended veterinary guidelines and maximum levels of exposure for wild vultures (estimated as 1.54 mg kg −1 ). Doses were administered by oral gavage or through feeding tissues from cattle dosed with ketoprofen at 6 mg kg −1 cattle body weight, before slaughter. Mortalities occurred at dose levels of 1.5 and 5 mg kg −1 vulture body weight (within the range recommended for clinical treatment) with the same clinical signs as observed for diclofenac. Surveys of livestock carcasses in India indicate that toxic levels of residual ketoprofen are already present in vulture food supplies. Consequently, we strongly recommend that ketoprofen is not used for veterinary treatment of livestock in Asia and in other regions of the world where vultures access livestock carcasses. The only alternative to diclofenac that should be promoted as safe for vultures is the NSAID meloxicam.

Avian scavengers and the threat from veterinary pharmaceuticals

“…However, to the best of our knowledge, carprofen is not used in India and flunixin is administered infrequently [26]. The only other NSAID thought to have a high potential to cause mortality in Gyps vultures in India is ketoprofen [33]. However, the emergence of veterinary use of this drug in India came considerably later than the onset of the vulture declines (figure 2).…”

“…B 369: 20130574 in cattle [34] and is, perhaps as a result, rarely detected in livestock carcasses in India. It was detected in 0.8% of 1488 carcasses sampled in 2006 [12], although a few of these contained concentrations that might have been lethal [12,33].…”

Merging Wildlife and Environmental Monitoring Approaches with Forensic Principles: Application of Unconventional and Non-Invasive Sampling in Eco- Pharmacovigilance

“…Generally speaking, far more information is urgently needed regarding NSAIDs known or suspected to cause gout-related mortality (e.g. carprofen, ibuprofen, ketoprofen, flunixin, phenylbutazone) [112][113][114], no less so now that diclofenac has been registered for veterinary use in some parts of Europe, especially Spain. This will entail assessing the disposition of these agents in a relevant suite of agricultural animals, conducting safety trials with vultures (or a vulture cell line) and actively monitoring for residue levels in livestock carcasses.…”

The toxicokinetics of ketoprofen in Gyps coprotheres: toxicity due to zero-order metabolism

“…These doses were based upon the lower and upper ranges of doses recommended for the clinical treatment of birds (Pollock et al 2005) and were also representative of the range of doses that vultures could receive in the wild if they fed upon carcasses of livestock that had been dosed with ketoprofen in the hours before death (Naidoo et al 2010). At 5 mg/kg, 7 out of 11 birds died with typical signs previously associated with diclofenac toxicity, i.e.…”

“…In an attempt to investigate the safety of ketoprofen in Gyps, we exposed adult captive non-breeding Cape GriVons (G. coprotheres) to doses of either 1 mg/kg or 5 mg/kg (n = 5 and 11 birds, respectively) of ketoprofen (Naidoo et al 2010). These doses were based upon the lower and upper ranges of doses recommended for the clinical treatment of birds (Pollock et al 2005) and were also representative of the range of doses that vultures could receive in the wild if they fed upon carcasses of livestock that had been dosed with ketoprofen in the hours before death (Naidoo et al 2010).…”