March 2016: Cattle metabolise aceclofenac into vulture-killing diclofenac

Veterinary use on cattle of the non-steroidal anti-inflammatory drug (NSAID) diclofenac is the principal cause of the virtual disappearance of formerly abundant vultures from most parts of the Indian subcontinent. Vultures die from kidney failure when the feed on the carcass of an animal given the drug shortly before it died. The population of one species, the oriental white-backed vulture, has declined to one-thousandth of what it was before diclofenac came into widespread use in the 1990s. Veterinary use of diclofenac was banned in India, Nepal and Pakistan in 2006 to protect vultures, but several other NSAIDs of unknown toxicity to vultures are now sold legally in its place. Today, in an article accepted for publication in Conservation Biology, SAVE (Savings Asia’s Vultures from Extinction) partners show that cattle quickly metabolise one of these drugs, aceclofenac, into vulture-killing diclofenac.

The RSPB Centre for Conservation Science, in collaboration with the Department of Paraclinical Sciences (University of Pretoria), the Environmental Research Institute (University of the Highlands and Islands) and others, gave four cattle the recommended veterinary dose of aceclofenac, sampled their blood at intervals and analysed the samples to measure concentrations of aceclofenac and diclofenac.

The results were clear: the cattle rapidly metabolised almost all of the aceclofenac into diclofenac. The area under the plasma concentration versus time curve (a standard measure of drug absorption and elimination) for the diclofenac-metabolite was more than 10 times that of aceclofenac.

The ramifications of this finding are serious because aceclofenac is widely and legally available for treating livestock in South Asia. It is recommended for the same uses as diclofenac, including palliative care of dying cattle, which leads to the contamination of carcasses. According to repeated surveys of drugs offered for sale for veterinary use in pharmacies its availability is increasing.

“A cow treated with aceclofenac poses the same threat to Gyps vultures as one treated with diclofenac. Aceclofenac soon becomes diclofenac,” remarked Toby Galligan, the lead author of the paper.

Fortunately, aceclofenac is not yet as popular as diclofenac once was. However, the Government of India’s ban on veterinary diclofenac in 2006, which reduced its use by more than half, and an amendment to that ban in 2015, which is hoped to reduce diclofenac use even further, may result in increases in aceclofenac use, particularly if pharmaceutical companies promote it as a legal and harmless substitute for diclofenac.

At present, vulture populations have stopped declining after the decrease in illegal diclofenac use, but these magnificent birds may now be pushed over the brink by an increase in legal aceclofenac use.

Four years ago, in the “Delhi Declaration” (Regional Declaration on the Conservation of South Asia’s Critically Endangered Vulture Species: 4 May 2012), the governments of Bangladesh, India, Pakistan and Nepal agreed to prevent veterinary use of aceclofenac so as to protect vultures. However, nothing has been done so far to impellent this commitment because, whilst aceclofenac was known to be metabolised to diclofenac in several mammal species, this had not been demonstrated in cattle. This study removes any reason to delay further. Responsible governments should immediately ban all aceclofenac formulations that can be used for treating cattle. Such a ban needs to be comprehensive, covering the manufacture, importation, retail and use of all but single dose vials for human health care. Further, bans should be established even where aceclofenac is uncommon or not currently available.

The governments of South Asia took strong and swift action against diclofenac to save their vultures and promised it for aceclofenac too. Now, it is time for them to take equally strong and swift action against aceclofenac. The alternative relaxed approach – as we have seen in the European Union with the recent approval of veterinary diclofenac there that now threatens Europe’s vultures – could be the final straw for the endemic vulture species of South Asia.

“The ultimate problem is that nowhere in the world are pharmaceutical drugs, whether for human or animal use, safety tested on the wildlife that are exposed to them before approval is given to use them” said Dr Galligan.

“We have known for over a decade that some drugs are toxic to vultures and that vultures are exposed to these drugs through the consumption of contaminated carcasses; but still there is no mandatory safety testing for such drugs before legal approval, nor a clear legislative mechanism to have these drugs banned. This is true for South Asian nations as well as the EU.”

Read the paper and a blog about it.

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