Pharmacokinetic Profile of Doxycycline in Koala Plasma after Weekly Subcutaneous Injections for the Treatment of Chlamydiosis

Abstract

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.