Pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation of cefquinome in llamas, following intravenous, intramuscular and subcutaneous administration in serum and tissue cage fluid

HIMELFARB, M. A.; ZARAZAGA, M. P.; SAN ANDRÉS, M. I.; LORENZUTTI, A. M; AGUILAR, S.; RUBIO-LANGRE, S. ; LITTERIO, N. J.; DE LUCAS, J.; HIMELFARB, M. A.; ZARAZAGA, M. P.; SAN ANDRÉS, M. I.; LORENZUTTI, A. M; AGUILAR, S.; RUBIO-LANGRE, S. ; LITTERIO, N. J.; DE LUCAS, J.

JOURNAL OF SMALL RUMINANT RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 p. 134 - 140

0921-4488

The objective of this study was to determine the pharmacokinetic behavior of cefquinome (CFQ) in serumand tissue cage fluid (TCF) in llamas, after intravenous (IV), intramuscular (IM) and subcutaneous (SC)administration of 2 mg/kg. Two tissue cages (TC) per animal were implanted in the subcutaneous tis-sue, on the pectoralis major muscles area. Serum and TCF concentrations of CFQ were determined bymicrobiological assay using Klebsiella pneumoniae ATCC 10031 as the test microorganism. Minimuminhibitory concentrations (MIC) of CFQ against Escherichia coli and Staphylococcus aureus strains isolatedfrom llamas were determined by broth microdilution method. S. aureus ATCC 29213 and E. coli ATCC25922 strains were used as controls. Finally, a pharmacokinetic/pharmacodynamic (PK/PD) analysis byMonte Carlo simulation, based on pharmacokinetic data obtained from IV, IM and SC administration ofCFQ in llamas and MIC values, was carried out to evaluate the antimicrobial efficacy of the dose regi-men. CFQ showed a limited distribution, with values of Vdss = 0.10 ± 0.01 and Vz = 0.18 ± 0.04L/kg. Totalbody clearance (0.05 ± 0.01 L*kg/h) was lower than reported in other species. Absolute bioavailabilityof IM and SC routes was complete (124 ± 45% and 94 ± 35%, respectively). Moreover, CFQ presented aAUCTCF/AUCserumratio MIC values, resultingin a better antimicrobial efficacy of CFQ in this biological compartment. MIC90values for E. coli and S.aureus were 0.06 g/mL and 0.50 g/mL, respectively, with a MIC90/MIC50= 2. Based on the PK/PD anal-ysis, a dose regimen of CFQ of 2 mg/kg q12 h by IV, IM and SC routes, could be effective for the treatmentof infections caused by pathogens with MIC values ≤0.50 g/mL. Therefore, CFQ appears to be a goodchoice against E. coli and S. aureus in llamas.