Elimination of tilmicosin in lactating ewes.

Tilmicosin was injected subcutaneously to lactating ewes once at a dose of 10 mg kg(-1) b.wt. to determine its plasma, milk, urine and ruminal juice c oncentrations. Tilmicosin could be detected in all those fluids 30 minutes after injection. Milk and urine concentrations were higher than those of pl asma and ruminal juice. The drug was detectable in milk, urine and plasma f or 9, 4 and 3 days after injection, respectively. No amount of tilmicosin c ould be detected in ruminal juice 12 hours following administration. The me an peak concentration of tilmicosin in plasma and milk (C-max) were 1.29 an d 9.5 mu g ml(-1) and were obtained at (T-max) 5.235 and 15.093 hours, resp ectively. The drug was slowly eliminated from plasma and milk as indicated by its long half-life (t(1/2el)) of 15.4 and 26.2 hours, respectively. The mean binding of tilmicosin to plasma and milk proteins in vitro was 16. 8 % and 26.8 %, respectively. The drug was not bound to ruminal juice at an y extent. The rate of tilmicosin renal clearance revealed that it was corre spondingly increased with higher blood concentrations. While creatinine cle arance showed no significant change after tilmicosin administration. The ra tio (fractional clearance) between tilmicosin renal clearance to creatinine clearance was less than one indicating that the glomerular filtration is t he main pathway of elimination through kidneys. The rate of ruminal gas fermentation in ewes was inhibited after subcutaneo us injection of tilmicosin at a dose of 10 mg kg(-1) b.wt. The tested sampl es taken at different time intervals from the rumen of ewes showed a subseq uent reduction in the rate of fermentation as compared to control samples. The reduction was correspondingly increased with the increase of tilmicosin concentration in ruminal juice and returned to normal thereafter.