Pharmacokinetic evaluation of marbofloxacin after intravenous administration at different ages in llama crias, and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation.

Abstract

In llama crias (tekes), Escherichia coli and Staphylococcus aureus are major pathogens, and marbofloxacin could be a suitable choice. The objectives of this study were (a) to evaluate the serum pharmacokinetics of marbofloxacin (5mg/kg) after intravenous administration in tekes and simulate a multidose regimen; (b) to emulate pharmacokinetic profiles after single dose and steady-state conditions by Monte Carlo simulation (c) to determine the MIC of regional strains of Escherichia coli and Staphylococcus aureus; (d) to perform a PK/PD analysis by Monte Carlo simulation. Pharmacokinetics of marbofloxacin was evaluated in six animals at 3, 10, 24, 50, and 80days after birth. Marbofloxacin were determined by HPLC. A steady-state multi-dose simulation was carried out, and concentration-time profiles were generated by Monte Carlo simulation. MIC of marbofloxacin against regional E.coli and S.aureus strains were also determined. Finally, a PK/PD analysis was conducted by Monte Carlo simulation. After pharmacokinetic analysis, clearance showed a trend to increase (0.14 and 0.18L kg-1 hr-1 ), and AUC (36.74 and 15.21μg hr-1 ml-1 ) and Vss (3.06 and 3.37L/kg) trended to decrease at 3 and 80days-old, respectively, showing accumulation ~50% in animals with 3days. All strains tested of E.coli (MIC90 =0.06μg/ml) and S.aureus (MIC90 =0.25μg/ml) were susceptible to marbofloxacin. PK/PD analysis suggests that the therapeutic regimen of marbofloxacin could be effective for infections caused by E.coli strains in animals between 3 and 80days, with a CFR for Cmax /MIC>10 of 100% and for AUC24 /MIC>125 of 99.99%; and for infections produced by S.aureus in animals between 3 and 24days old, with a CFR for Cmax /MIC>10 of 93.08% and for AUC24 /MIC>60 of 97.01%, but a higher dose should be used in older animals, because PK/PD endpoints were not met.