A pharmacokinetic analysis of tylosin in the normal dog

Studies were conducted to determine certain kinetic variables for tylosin in the normal dog. These variables were determined by pharmacokinetic analysis, measuring the decrease in serum concentration of tylosin activity in 3 separate experiments. Tylosin, given as a single intravenous dose of 10 mg of tylosin activity/kg of body weight, was calculated to have an elimination half life (t1/2beta) of 54 minutes and was no longer detectable in the serum by assay methods at about 270 minutes. In addition, tylosin appeared to be highly distributed with an apparent volume of distribution of about 1.7 L/kg and a tissue-to-plasma ratio of about 0.7. The body clearance of tylosin was calculated to be about 22 ml/kg minute. A separate multiple-dose intravenous experiment with the same dose per injection was conducted and showed similar results. Also, single intramuscular injection of 10 mg of tylosin activity/kg showed tylosin to peak after injection in the serum at 30 minutes, attaining a concentration of approximately 1.5 mug/ml. This concentration was maintained through 60 minutes and decreased slowly through 540 minutes. Data generated through 17 clinical cases indicated that the minimum inhibitory concentration for tylosin in Pasteurella spp tested was about 6.25 mcs/ml and for hemolytic Staphylococcus spp tested greater than or equal to 0.4 mug/ml. Thus, it would appear that tylosin, given at the recommended dose (6.6 to 11.0 mg tylosin activity/kg of body weight once or twice per day), would produce serum levels insufficient to treat all Pasteurella spp and some hemolytic Staphylococcus spp tested since a serum level of tylosin at slightly higher than 1 mug/ml for about 30 minutes was achieved in this study.