Details

Autor(en) / Beteiligte

• Serrano-Rodríguez, Juan Manuel
• Fernández-Varón, Emilio
• Rodríguez, Carlos Mario Cárceles
• Andrés-Larrea, Manuel Ignacio San
• Rubio-Langre, Sonia
• de la Fe, Christian
• Dova, Samanta Waxman
• Bhardwaj, Pallavi
• Sidhu, Pritam Kaur
• Litterio, Nicolás Javier
• Lorenzutti, Augusto Matías

Titel

Population pharmacokinetics and pharmacokinetic/pharmacodynamic evaluation of marbofloxacin against Coagulase-negative staphylococci, Staphylococcus aureus and Mycoplasma agalactiae pathogens in goats

Ist Teil von

• Research in veterinary science, 2023-06, Vol.159, p.1-10

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Marbofloxacin is a broad-spectrum fluoroquinolone, and an extra-label use has been reported in horse, sheep and goat. However, extrapolation of dosage regimens from cattle to horse and small ruminants could lead to incorrect dosing due to pharmacokinetic differences among species, increasing the risk of antimicrobial resistance or toxicity. Pharmacokinetic properties of marbofloxacin, including PK/PD analysis, have been studied by intravenous, intramuscular and subcutaneous administration in lactating and non-lactating goats. A population pharmacokinetic model of marbofloxacin in goats was built using 10 pharmacokinetic studies after intravenous, intramuscular, and subcutaneous administration at a dose of 2, 5 and 10 mg/kg. Serum or plasma and milk concentration-time profiles were simultaneously fitted with a non-linear mixed effect model with Monolix software. Level of milk production (lactating and non-lactating) and health status (healthy and un-healthy) were retained as covariates on volume of distribution and clearance. Marbofloxacin concentrations were well described in plasma/serum and milk by the population model. Simulated dose regimens of marbofloxacin administered at 2, 5 and 10 mg/kg by intramuscular route for five days were evaluated (n = 5000 per group). Steady-state fAUCs for each dose regimen were obtained. Probability of target attainment of fAUC/MIC ratios were determined and PK/PDco values (highest MIC for which 90% of individuals can achieve a prior numerical value of the fAUC/MIC index) were established using Monte Carlo simulations (n = 50,000). MIC values for wild type isolates of Staphylococcus aureus, coagulase negative staphylococci, and Mycoplasma agalactiae were determined and tentative epidemiological cutoff (TECOFF) were obtained at 1.0, 0.5 and 0.5 mg/L, respectively. The PK/PDco for the dose regimen of 2 mg/kg/24 h and 5 mg/kg/24 h (0.125 and 0.25 mg/L) were lower than TECOFF (0.5 and 1 mg/L). The dosage regimen of 10 mg/kg/24 h was adequate for intermediate MIC values of 0.125–0.50 mg/L and could be effective for a population with a target fAUC/MIC ratio ˂ 48 for Coagulase negative staphylococci and Mycoplasma agalactiae, but not for Staphylococcus aureus. Results obtained in this study could be taken as a starting point by committees that set the clinical breakpoints and justifies expert rules to optimize marbofloxacin dose regimens. [Display omitted] •A POP-PK model of marbofloxacin in goats after IV, IM, and SQ administrations at 2, 5 and 10 mg/kg was conducted.•Dose regimens of marbofloxacin were simulated and probability of target attainment was determined by Monte Carlo simulation.•MIC of Staphylococcus aureus, coagulase negative staphylococci and Mycoplasma agalactiae isolates from goats were determined.•Tentative epidemiological cutoff (TECOFF) and pharmacokinetic-pharmacodynamic fAUC/MIC ratios were obtained and investigated.•5 mg/kg/24h and 10 mg/kg/24h achieved fAUC/MIC ratios of 30 and 55, and could be taken for further clinical trials in goats.