Evaluation of enrofloxacin use in koalas (Phascolarctos cinereus) via population pharmacokinetics and Monte Carlo simulation.
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.
Faculty of Veterinary Science, The University of Sydney, Camperdown, NSW, Australia.
L A
LA
Black
C B
CB
Landersdorfer
J B
JB
Bulitta
J E
JE
Griffith
M
M
Govendir
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006207:Half-Life; D008297:Male; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D048368:Phascolarctidae / Q000097:blood / Q000378:metabolism*; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin