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

Autor: Serrano-Rodríguez JM; Pharmacology Area, Department of Nursing, Pharmacology and Physiotherapy, Faculty of Veterinary Medicine, University of Córdoba, Spain. Electronic address: jserranor@uco.es., Fernández-Varón E; Center for Biomedical Research (CIBM), Department of Pharmacology, University of Granada, Spain. Electronic address: emiliofv@ugr.es., Rodríguez CMC; Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Spain. Electronic address: carceles@um.es., Andrés-Larrea MIS; Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain. Electronic address: misanand@vet.ucm.es., Rubio-Langre S; Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Spain. Electronic address: sonrubio@ucm.es., de la Fe C; Department of Animal Health, Faculty of Veterinary Medicine, University of Murcia, Spain. Electronic address: cdelafe@um.es., Dova SW; Department of Anesthesiology, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina., Bhardwaj P; Department of Veterinary Pharmacology and Toxicology, DGCN College of Veterinary and Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, H.P., India. Electronic address: bpallavi@hillagric.ac.in., Sidhu PK; Pharmacokinetics, Drug Safety & DMPK, Boehringer Ingelheim Animal Health USA Inc., North Brunswick, NJ 08902. Electronic address: pritam.sidhu@boehringer-ingelheim.com., Litterio NJ; Facultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Católica de Córdoba, Argentina. Electronic address: nlitterio@ucc.edu.ar., Lorenzutti AM; Facultad de Ciencias Agropecuarias, IRNASUS CONICET-Universidad Católica de Córdoba, Argentina. Electronic address: matiaslorenzutti@ucc.edu.ar.
Jazyk: angličtina
Zdroj: Research in veterinary science [Res Vet Sci] 2023 Jun; Vol. 159, pp. 1-10. Date of Electronic Publication: 2023 Apr 03.
DOI: 10.1016/j.rvsc.2023.03.026
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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