Tilmicosin antibacterial activity and pharmacokinetics in cows

The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 112 Staphylococcus aureus isolates from the bovine udder was 0.78 μg/mL and 149 of 164 (90.8%) other gram‐positive udder pathogens were inhibited by tilmicosin concentrations < 3.12 μg/mL. The MIC of the drug for 19 of 22 S. aureus isolates was < 0.78 μg/mL when the test was conducted using Mueller‐Hinton (MH) agar or MH agar containing 7.5% skimmed milk. Acute cardiac toxicity followed intravenous (i.v.) injection of the drug at 10 mg/kg to 3 cows, but animals appeared clinically normal within 30 min after treatment. The pharmacokinetics of i.v.‐administered tilmicosin is typical for the macrolide class of antibiotics, i.e. low serum drug concentrations and a large volume of distribution (> 2.0 L/kg). The elimination half‐life ( t 1/2β values for 3 cows were 46.4. 56.0 and 72.8 min. The drug was administered subcutaneously (s.c.) to 5 cows at 10 mg/kg; the elimination half‐life ( t 1/2el ) was 4.18 ± 0.55 h and the mean s.c. bioavailability was 22%. Rapid and extensive penetration of tilmicosin from blood into milk, and slow elimination from the milk were among the characteristic kinetic features of the drug after i.v. and s.c. administration. Tilmicosin was injected s.c. at 10 mg/kg once to 9 cows after the last milking of lactation; dry udder secretion samples were collected daily for 11 consecutive days and assayed microbiologically. Concentrations of drug > 0.78 μg/mL were found in the secretion for 8–9 days after dosing. Systemic side‐effects were not observed after s.c. drug administration.