Drug Metabolism and Disposition in Australian Marsupial Koala (Phascolarctos cinereus)

Aims: Koalas are unique obligated eucalyptus feeding Australian marsupials that often require medical treatments after wildlife rehabilitation across Australia. At present, little is known about the pharmacology and pharmacokinetics of drugs commonly used in koalas and how koalas handle and detoxify toxic chemicals from both environmental exposure and their unique eucalyptus diet. The aim of this study is to summarise and critically evaluate the current literature on what is known about the pharmacokinetics (absorption, distribution, metabolism, and excretion ADME) of drugs frequently used in koalas, including antibiotics fluoroquinolones, fluconazole, chloramphenicol and analgesics. Methodology: Literature regarding drug disposition and pharmacokinetic studies of therapeutic agents commonly used in koalas over the last decade has been critically reviewed. Some older sources from the primary literature search have also been included to determine the background information leading to current rationale behind drug indication, dosage, and route of administration in marsupial koalas and related species. Results: Most studies reported a much lower bioavailability of orally administered drugs in koalas compared to that in humans and other species. Current dosing regimens do not prove to be effective or optimal in order to achieve the best treatment outcomes. It seems likely that oral administration of many drugs in koalas exhibited poor bioavailability due to poor absorption and might be extensive metabolism via hepatic and intestinal enzymes. Conclusion: Collectively, the findings suggest the need for further pharmacokinetic studies to investigate alternative routes of administration for many commonly used drugs in marsupial koalas, including antibiotics, anaesthetics, and analgesic medicines.

Quantitation of meloxicam in the plasma of koalas (Phascolarctos cinereus) by improved high performance liquid chromatography

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.

Quantitation of meloxicam in the plasma of koalas (Phascolarctos cinereus) by improved high performance liquid chromatography

An improved method to determine meloxicam (MEL) concentrations in koala plasma using reversed phase high performance liquid chromatography equipped with a photo diode array detector was developed and validated. A plasma sample clean-up step was carried out with hydrophilic-lipophilic copolymer solid phase extraction cartridges. MEL was separated from an endogenous interference using an isocratic mobile phase [acetonitrile and 50 mM potassium phosphate buffer (pH 2.15), 45:55 (v:v)] on a Nova-Pak C18 4-microm (300 x 3.9 mm) column. Retention times for MEL and piroxicam were 8.03 and 5.56 min, respectively. Peak area ratios of MEL to the internal standard (IS) were used for regression analysis of the calibration curve, which was linear from 10 to 1,000 ng/mL (r2 > 0.9998). Average absolute recovery rates were 91% and 96% for MEL and the IS, respectively. This method had sufficient sensitivity (lower quantitation limit of 10 ng/mL), precision, accuracy, and selectivity for routine analysis of MEL in koala plasma using 250-microL sample volumes. Our technique clearly resolved the MEL peak from the complex koala plasma matrix and accurately measured MEL concentrations in small plasma volumes.