Rapid and Prolonged Distribution of Tulathromycin into Lung Homogenate and Pulmonary Epithelial Lining Fluid of Holstein Calves Following a Single Subcutaneous Administration of 2.5 mg/kg Body Weight

Twenty-four healthy Holstein calves received single subcutaneous injections of 2.5 mg/kg bw tulathromycin. At each of 8 time points ranging from 1 - 360 hr post-dose, three animals were randomly selected for euthanasia. At the time of euthanasia, whole blood, lung tissue, and broncho-alveolar lavage (BAL) samples were collected and subsequently assayed for tulathromycin with an LC MS/MS procedure. Concentrations of tulathromycin in pulmonary epithelial lining fluid (PELF) were determined from the BAL supernatant concentrations using the urea dilution method. Concentrations of tulathromycin in the cells of the pulmonary epithelial lining fluid (PELF cells, predominately macrophages) were also determined. Tulathromycin distributed rapidly and extensively into PELF, PELF cells, and lung homogenate, with areas under the concentration-time curve through 360 hr (AUC(0-360)) that were 53 - 565 times the plasma AUC(0-360). Tulathromycin concentrations exceeded 1,000 ng/mL in PELF and 1,000 ng/g in lung homogenate by 3 hr post-dose, and the peak concentration in BAL cells was 19,500 ng/mL at 72 hr. The drug was slowly eliminated from lung homogenate, PELF, and PELF cells, with apparent t(1/2) values > 200 hr. These data demonstrate rapid achievement and prolonged maintenance of therapeutic tulathromycin concentrations at sites of respiratory infections in cattle following a single-dose administration.