Aspects of the pharmacokinetics and pharmacodynamics of chloramphenicol, enrofloxacin and fluconazole in koalas (Phascolarctos cinereus)

Abstract

In Australia, thousands of koalas receive medical treatment annually, mostly due to trauma and disease. The most common disease affecting koalas is chlamydiosis, responsible for debilitating conjunctivitis and urogenital disease. Cryptococcosis occurs less commonly, and is often fatal. Information regarding the pharmacokinetics and pharmacodynamics of commonly used drugs in koalas is lacking. The information available indicates koalas may have highly developed barriers to oral drug absorption, and an ability to rapidly metabolise and eliminate drugs following administration; these mechanisms probably evolved due to the koala’s highly toxic Eucalyptus spp. diet. The pharmacokinetics of chloramphenicol and enrofloxacin are investigated, and in vitro susceptibility testing of these drugs against koala isolates of Chlamydia pecorum is undertaken. Chloramphenicol and enrofloxacin are eliminated at similar rates to other mammals. Chloramphenicol is found to be a potential treatment option for koala chlamydiosis, although slight dosage adjustments may be necessary. Enrofloxacin is found to be unsuitable for treating chlamydiosis in koalas. It may, however, be useful in treating other bacterial infections. The pharmacokinetics of fluconazole as a treatment option for cryptococcosis are also investigated. Findings include poor and variable oral absorption, rapid elimination, and absorption rate-limited disposition following oral administration; these findings contrast the pharmacokinetics of fluconazole in other species. Fluconazole is unlikely to be successful in treating cryptococcosis at currently used dosages. When the findings presented in this thesis are viewed within the context of the metabolic pathways of these drugs in other species, hypotheses regarding the capacity of these metabolic pathways in koalas can be formed, and speculation can be made regarding the types of drugs that are likely to display favourable pharmacokinetic profiles in koalas.