Image courtesy Taronga Zoo
Some of my research is to work out the best medicines and their dosage for koalas and other species.
Koalas are unique animals because they eat only eucalyptus leaves, so their bodies are very efficient and getting rid of toxic substances. Thus koalas eliminate some medicines such as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) very quickly, so quickly in fact that they do not have a therapeutic effect.
So how do I do these studies to know that NSAIDs do not last for long when eliminated in koalas?
I can do this without using live koalas. Which is great news!
I use what is called an in-vitro microsome model. I extract the metabolism enzymes found in the liver. These enzymes (called microsomes) are taken from koalas who have died from other causes, such as the koala has been hit by a car, or attacked by a dog or a feral animal etc. These enzymes can be stored for several years in a very cold freezer.
If I want to test the rate of elimination of a NSAID in the koala, I do a comparative species study. That is, I run the study investigating the rate of depletion of the NSAID not only using the enzymes from the koala, but also the ring-tailed possum, brush-tailed possum, cat, dog and rat. I incubate the NSAID with the microsomes, making a ‘medicine and microsome soup’. This soup is kept at body temperature ( 37 ° C) and I take a sample and analyse the NSAID concentration at the very beginning of the incubation with the microsomes, this is the time = 0 minute sample. Then I might take a sample from the soup at 30 minute intervals thereafter and analyse the concentration of NSAID left in the soup. If the NSAID in the time = 0 minute sample has most of the NSAID, I can then workout a percentage of how much of the NSAID is left at 30 minutes by
NSAID concentration at 30 minutes / NSAID concentration at 0 minutes as a %.
I can then plot this % of NSAID depletion by the enzymes of each species.
A few weeks ago I said that the NSAID carprofen was depleted very quickly by koala metabolism enzymes
This graph shows the carprofen is eliminated quickest by the koala and brush-tailed possum, followed by the ring-tailed possum and then by the dog, cat and rat. This work was done by Juan Lillo. The graph
We saw this same pattern when we used this model to look at the rate of meloxicam deletion in the same species.
It is a very useful model as it is not done in live animals ! Which is a very good thing. When possible I try to avoid using the live animal for our studies.