Study into selected antimicrobial drugs for koalas (Phascolarctos cinereus), incorporating consideration of koalas’ endogenous plasma and serum antibacterial activity

Abstract

Pharmacokinetic studies of some drugs in koalas argue that traditional ad-hoc dosage extrapolation from dogs and cats to koalas is inappropriate. This research describes plasma concentration changes of cefovecin and amoxicillin in koalas. Posaconazole was also investigated as its broad-spectrum antifungal activity might be efficacious against cryptococcosis in koalas. HPLC methods to determine plasma concentrations of these antimicrobials were developed and validated. Posaconazole was administered at 3 mg/kg to two koalas i.v. and 6 mg/kg to six koalas p.o. Posaconazole is predicted to be efficacious for cryptococcosis treatment in koalas. An in-vitro study to determine cefovecin binding to plasma proteins of koalas and some Australian marsupials demonstrated the proportion of binding between 12 to 40 %, suggesting the elimination half-life of cefovecin in these species is likely to be shorter than those in dogs and cats. Cefovecin was administered as a single bolus (8 mg/kg) to six koalas s.c. Cefovecin plasma concentrations at all time points (0 to 96 h) in all animals were below 1 μg/mL, indicating cefovecin has a short duration of action in koalas. Amoxicillin was administered to six koalas at 10 mg/kg s.c. Low concentrations of amoxicillin were detected; however, drug instability might have contributed towards these findings. Bioassays were undertaken to confirm amoxicillin and cefovecin HPLC results. The bioassays demonstrated variable plasma antibacterial activities at t = 0 h (before koalas were medicated). Consequently, endogenous antibacterial activities of koala plasma and serum to inhibit E. coli and S. aureus were evaluated. Koala blood matrices demonstrated significant variations in inhibiting both pathogens’ growth compared to other species studied. Reasons for such variations were unclear but opened a new area for investigating koalas’ endogenous antimicrobial activity and how it might protect this ‘vulnerable’ species from infectious diseases.