Pharmacokinetics of azithromycin in lactating dairy cows with subclinical mastitis caused by Staphylococcus aureus
2010
LUCAS, M.F. | ERRECALDE, J.O. | MESTORINO, N.
Azithromycin is a time-dependent antimicrobial with long persistence. The main characteristics of azithromycin suggest that it could be useful for treating bovine mastitis caused by Staphylococcus aureus. To investigate this possibility, its pharmacokinetic (PK) behavior was studied. Six Holstein lactating cows with subclinical mastitis were administered two 10 mg/kg intramuscular (i.m.) doses of azithromycin, with a 48-h interval. Milk and plasma concentrations were measured by microbiological assay. The MIC₉₀ was determined in 51 S. aureus isolations to calculate pharmacokinetic/pharmacodynamic (PK/PD) parameters. Milk maximal concentration (Cmax) was 7.76 ± 1.76 μg/mL (16.67 h post-first administration) and 7.82 ± 2.18 μg/mL (14 h post-2nd administration). In plasma Cmax was 0.18 ± 0.03 μg/mL (2 h post-1rst administration) and 0.11 ± 0.03 μg/mL (14 h post-2nd administration). Azithromycin was eliminated from the milk with a half-life (T[fraction one-half]λ) of 158.26 ± 137.7 h after 2nd administration, meanwhile plasma T[fraction one-half]λ resulted shorter(13.97 ± 11.1 h). The mean area under the concentration vs. time curve from 0 to 24 h (AUC₀₋₂₄h₎ was 153.82 ± 34.66 μg·h/mL in milk secretion and 2.61 ± 0.59 μg·h/mL in plasma. Infection presence in the quarters had a significant effect (P < 0.05) on the area under the concentration vs. time curve from 0 to infinity (AUC₀₋[infinity]) and clearance from the mammary gland (Clmam/F). Moreover, it had influence on milk bioavailability (Fmilk), T[fraction one-half]λ, AUC₀₋[infinity] and mean residence time (MRT) in milk, which values resulted increased in mastitic quarters. In this study, it was determined that the production level and the mammary health status have an influence on PK parameters of azithromycin treatments in bovine mastitis.
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