Pharmacokinetics of a new parenteral formulation of tilmicosin-La in cows

The blood serum pharmacokinetics of a poloxamer-407 based new pharmaceutical preparation of 39% tilmicosin was determined in cows. two dose levels injected sc,were assessed: 10 mg/kg (til-la10) and 26 mg/kg (til-la26). tilmicosin was determined using hplc,also electrocardiographic (ekg) monitoring in all animals before and at 1,2 and 4 h after the injection of the drug was performed to measure key ekg parameters,including heart rate. maximum serum concentration values were 2.6 μg/ml and 1.23 μg/ml,occurring 4.9 and 5.1 h after the injection of til- la26 and til-la10,respectively. mean residence time was statistically larger for til-la26 (50.4±5.8 h) than til-la10 (37.4±4.7 h) (p<0.05),with t1/2el of 39.8 h for til-la26 and 33.2 h for til-la10. there were no differences in relative bioavailability as adjusted for dose (aumc of 8663 μg/mlžh2 for til-la26 and 2858 μg/mlžh2 for til-la10). this new formulation as dosed for til-la26possesses a long t1/2el of tilmicosin and resulted in a lack of changes in the ekg and heart rate. based on pk/pd ratios tilmicosin is regarded as a time-dependent antibacterial drug. considering a theoretical minimum therapeutic serum concentration (mtc) of 0.1 μg/ml useful concentrations can be achieved for up to 192 h with til-la26 and an auc/mtc ratio of 1514 without cardiac toxicity. further studies are necessary to correlate pk/pd parameters obtained with clinical efficacy and a more thorough analysis of cardiac toxicity is required to determine the suitability of this preparation in bovine medicine. © 2015 pvj.