Featured image courtesy of Taronga Zoo, Mosman, NSW, Australia

This study was undertaken by Juan Lillo for his candidature for a Masters of Philosophy. Merran Govendir, Kong Li and Benjamin Kimble supervised Juan and this project.

 

We previously reported that the NSAID meloxicam (Metacam®) is rapidly metabolised  in the koala (Kimble, Black et al., 2013). Meloxicam has a half-life [1] of < 2 hours in koalas.  So much so, that to provide a reasonable duration of analgesia and / or an anti-inflammatory effect meloxicam would need to be administered approximately 3 to 4 times over a 24 hour period.

So we are trying to find a non-steroidal anti-inflammatory drug (NSAID) that has a longer duration of action than meloxicam, in the koala. That is why we investigated what is happening with carprofen, which is another veterinary NSAID. In Australia carprofen is registered for use in dogs, cats and horses. Some of carprofen’s trade names in Australia are Carprieve®, Caprofen®, Prolet®, Rimadyl® and Tergive®.

Juan looked at the rate at which liver enzymes from the koala, common ring-tailed possum, the eastern ring-tailed possum, cat, dog and those from the rat metabolised carprofen. This means that the liver metabolism enzymes from each of the above species were incubated with carprofen for a specific period of time. Consequently, Juan could work out how quickly carprofen is metabolised in each of the species, by this in-vitro model.

Carprofen has a more complex metabolism pathway than meloxicam. In people and animals, meloxicam primarily undergoes a Phase I metabolism that is an oxidation reaction. However carprofen not only undergoes a phase I reaction but also undergoes the Phase II reaction of glucuronidation in the dog and the rat.

Juan showed that carprofen is metabolised faster in marsupial species compared to that with the feline, canine and rat microsomes as shown in the figure.

The figure compares the rate of metabolism of carprofen when incubated with liver enzymes of the koala, brush-tailed possum, ring-tailed possum and those of the cat, dog and rat. In-vitro means that the study was conducted with hepatic enzymes and was not conducted in the live animal.

Carprofen invitro clearance figure

The key observation of this study is that hepatic enzymes of the marsupial species metabolise carprofen quicker than that of those of the cat, dog and rat.

Like meloxicam in the koala, the data indicates that carprofen is also rapidly metabolised by the koala and the possums, much faster that by canine liver enzymes. It is recommended that carprofen is administered to the dog once a day, we think the metabolism of carprofen is at least three times faster in the koala, maybe faster. So koalas would probably need to be dosed with carprofen at least three times over 24 h. This can only be confirmed by undertaking clinical trials in the live koalas.

But we will continue to look for an anti-inflammatory drug that can be administered once, or at best twice, every 24 h and will provide some analgesia over this time span.

 

Acknowledgements

Thanks to Dr Fumie Tokonami and Currumbin Wildlife Hospital that provided the koala tissues used for this study. Thanks to the Port Macquarie Koala Hospital and the Winifred Violet Scott Charitable Foundation that provides financial support of Dr Kimble who provides technical advice and assistance to this study

 

[1] Half-life is the time taken for the drug concentration to decrease by 50%

Liver enzymes are collected from dead animals. No animals are killed for this research. The wildlife hospitals collect tissues from animals that have died due to being hit by cars or attacked by feral animals.