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oai:docta.ucm.es:20.500.14352/1125302025-08-22T13:22:58Zcom_20.500.14352_14col_20.500.14352_15

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. 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. 2024-12-12T13:00:59Z 2024-12-12T13:00:59Z 2024-12-12T13:00:59Z 2018 journal article 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 Wiley