Evaluation of enroﬂoxacin use in koalas (Phascolarctos cinereus) via population pharmacokinetics and Monte Carlo simulation
L. A. BLACK* C. B. LANDERSDORFER† J. B. BULITTA† J. E. GRIFFITH* & M. GOVENDIR*
*Faculty of Veterinary Science, The University of Sydney, Camperdown, NSW, Australia
†Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia
Clinically normal koalas (n = 6) received a single dose of intravenous enroﬂoxacin (10 mg/kg). Serial plasma samples were collected over 24 h, and enroﬂoxacin concentrations were determined via high-performance liquid chromatography. Population pharmacokinetic modeling was performed in S-ADAPT. The probability of target attainment (PTA) was predicted via Monte Carlo simulations (MCS) using relevant target values (30–300) based on the unbound area under the curve over 24 h divided by the minimum inhibitory concentration (MIC) (fAUC0–24/MIC), and published subcutaneous data were incorporated (Grifﬁth et al., 2010). A two-compartment disposition model with allometrically scaled clearances (exponent: 0.75) and volumes of distribution (exponent: 1.0) adequately described the disposition of enroﬂoxacin. For 5.4 kg koalas (average weight), point estimates for total clearance (SE%) were 2.58 L/h (15%), central volume of distribution 0.249 L (14%), and peripheral volume 2.77 L (20%). MCS using a target fAUC0–24/MIC of 40 predicted highest treatable MICs of 0.0625 mg/L for intravenous dosing and 0.0313 mg/L for subcutaneous dosing of 10 mg/kg enroﬂoxacin every 24 h. Thus, the frequently used dosage of 10 mg/kg enroﬂoxacin every 24 h subcutaneously may be appropriate against gram-positive bacteria with MICs ≤ 0.03 mg/L (PTA > 90%), but appears inadequate against gram-negative bacteria and Chlamydiae in koalas.