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Pharmacokinetic evaluation of marbofloxacin after intravenous administration at different ages in llama crias, and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation Rubio Langre, Sonia Aguilar Sola, Soledad Lorenzutti, Augusto Matías San Andrés Larrea, Manuel Ignacio Lucas Burneo, José Julio De Litterio, Nicolás J. 636.09:615 Llamas Marbofloxacin Monte Carlo simulation Pharmacodynamics Pharmacokinetics Farmacología veterinaria Ciencias Biomédicas 3109.08 Farmacología All authors have read and approved the final manuscript. S. R. L.: Design, acquisition, analysis and interpretation of data. S. A. S.: Acquisition, analysis and interpretation of data. A. M. L.: Analysis, interpretation of data and drafting the manuscript. M. I. S. A.: Design and critical revision of the manuscript for important intellectual content. J. J. D. L.: Acquisition, analysis of data and critical revision of the manuscript for important intellectual content. N. J. L.: Design and critical revision of the manuscript for important intellectual content. 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 (5 mg/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 80 days 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 0.18 L kg−1 hr−1), and AUC (36.74 and 15.21 μg hr−1 ml−1) and Vss (3.06 and 3.37 L/kg) trended to decrease at 3 and 80 days-old, respectively, showing accumulation ~50% in animals with 3 days. All strains tested of E. coli (MIC90 = 0.06 μg/ml) and S. aureus (MIC90 = 0.25 μg/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 80 days, 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 24 days 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. Universidad Complutense de Madrid Universidad Católica de Córdoba (Argentina) Sección Deptal. de Farmacología y Toxicología (Veterinaria) Fac. de Veterinaria TRUE pub 2024-12-12T13:00:59Z 2024-12-12T13:00:59Z 2018 journal article VoR https://hdl.handle.net/20.500.14352/112530 XXXX-XXXX 10.1111/jvp.12698 1365-2885 eng Rubio-Langre S, Aguilar-Sola S, Lorenzutti AM, San Andrés MI, De Lucas JJ, Litterio NJ. Pharmacokinetic evaluation of marbofloxacin after intravenous administration at different ages in llama crias, and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation. J vet Pharmacol Therap. 2018; 41: 861–870. https://doi.org/10.1111/jvp.12698 restricted access application/pdf Wiley