G. Ziv et al., TILMICOSIN ANTIBACTERIAL ACTIVITY AND PHARMACOKINETICS IN COWS, Journal of veterinary pharmacology and therapeutics, 18(5), 1995, pp. 340-345
The minimal inhibitory concentration (MIC) of tilmicosin for 90% of 11
2 Staphylococcus aureus isolates from the bovine udder was 0.78 mu g/m
L and 149 of 164 (90.8%) other gram-positive udder pathogens were inhi
bited by tilmicosin concentrations <2.12 mu g/mL. The MIC of the drug
for 19 of 22 S. aureus isolates was <0.78 mu g/mL when the test was co
nducted using Mueller-Hinton (MH) agar of MH agar containing 7.5% skim
med milk. Acute cardiac toxicity followed intravenous (i.v.) injection
of the drug at 10 mg/kg to 3 cows, but animals appeared clinically no
rmal within 30 min after treatment. The pharmacokinetics of i.v.-admin
istered 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(1/2 beta)) values for 3 cow
s were 46.4, 56.0 and 72.8 min. The drug was administered subcutaneous
ly (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 a
nd extensive penetration of tilmicosin from blood into milk, and slow
elimination from the milk were among the characteristic kinetic featur
es of the drug after i,v, and s.c. administration. Tilmicosin was inje
cted s.c, at 10 mg/kg once to 9 cows after the last milking of lactati
on; dry udder secretion samples were collected daily for 11 consecutiv
e days and assayed microbiologically. Concentrations of drug > 0.78 mu
g/mL were found in the secretion for 8-9 days after dosing. Systemic
side-effects were not observed after s.c, drug administration.