Evaluation of enrofloxacin use in koalas (Phascolarctos cinereus) via population pharmacokinetics andMonteCarlo simulation

Abstract

Clinically normal koalas (n=6) received a single dose of intravenous enrofloxacin (10mg/kg). Serial plasma samples were collected over 24h, 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 24h divided by the minimum inhibitory concentration (MIC) (fAUC0-24 /MIC), and published subcutaneous data were incorporated (Griffith etal., 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 5.4kg koalas (average weight), point estimates for total clearance (SE%) were 2.58L/h (15%), central volume of distribution 0.249L (14%), and peripheral volume 2.77L (20%). MCS using a target fAUC0-24 /MIC of 40 predicted highest treatable MICs of 0.0625mg/L for intravenous dosing and 0.0313mg/L for subcutaneous dosing of 10mg/kg enrofloxacin every 24h. Thus, the frequently used dosage of 10mg/kg enrofloxacin every 24h subcutaneously may be appropriate against gram-positive bacteria with MICs≤0.03mg/L (PTA>90%), but appears inadequate against gram-negative bacteria and Chlamydiae in koalas.