Pharmacokinetics of azithromycin in lactating dairy cows with subclinical mastitis caused by Staphylococcus aureus

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 (C-max) was 7.76 +/- 1.76 mu g/mL (16.67 h post-first administration) and 7.82 +/- 2.18 mu g/mL (14 h post-2nd administration). In plasma C-max was 0.18 +/- 0.03 mu g/mL (2 h post-1rst administration) and 0.11 +/- 0.03 mu g/mL (14 h post-2nd administration). Azithromycin was eliminated from the milk with a half-life (T1/2 lambda) of 158.26 +/- 137.7 h after 2nd administration, meanwhile plasma T1/2 lambda resulted shorter(13.97 +/- 11.1 h). The mean area under the concentration vs. time curve from 0 to 24 h (AUC(0-24h)) was 153.82 +/- 34.66 mu g center dot h/mL in milk secretion and 2.61 +/- 0.59 mu g center dot 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 (AUC(0-infinity)) and clearance from the mammary gland (Cl-mam/F). Moreover, it had influence on milk bioavailability (F-milk), T1/2 lambda, AUC(0-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.