Six mature, male koalas (Phascolarctos cinereus), with clinical signs of chlamydiosis, were administered doxycycline as a 5 mg/kg subcutaneous injection, once a week for four weeks. Blood was collected at standardised time points (T = 0 to 672 h) to quantify the plasma doxycycline concentrations through high-pressure liquid chromatography (HPLC). In five koalas, the doxycycline plasma concentration over the first 48 h appeared to have two distinct elimination gradients; therefore, a two-compartmental analysis was undertaken to describe the pharmacokinetic (PK) profile. The average ± SD maximum plasma concentration (Cmax) was 312.30 ± 107.74 ng/mL, while the average time ± SD taken to reach the maximum plasma concentration (Tmax) was 1.68 ± 1.49 h. The mean ± SD half-life of the distribution phase (T1/2 α) and the elimination phase (T1/2 β) were 10.51 ± 7.15 h and 82.93 ± 37.76 h, respectively. The average ± SD percentage of doxycycline binding to koala plasma protein was 83.65 ± 4.03% at three different concentrations, with a mean unbound fraction (fu) of 0.16. Using probability of target attainment modelling, doxycycline plasma concentrations were likely to inhibit 90% of pathogens with the doxycycline minimum inhibitory concentration (MIC) of 8.0-31.0 ng/mL, and the reported doxycycline MIC to inhibit Chlamydia pecorum isolates at the area under the curve/minimum inhibitory concentration (AUC/MIC) target of ≥24. All koalas were confirmed to be negative for Chlamydia pecorum using loop-mediated isothermal amplification (LAMP), from ocular and penile urethra swabs, three weeks after the last doxycycline injection.
Keywords: HPLC; Phascolarctos cinereus; chlamydiosis; doxycycline; koalas; pharmacokinetics.