No abstract

The performance characteristics of a newly developed liquid chromatography-mass spectrometry (LC-MS) method were validated and demonstrated to be fit for purpose in a pharmacokinetic and tissue depletion study of white-tailed deer and bison. Tulathromycin was extracted from bison and deer sera with acetonitrile or trifluoroacetic acid and K 2 HPO 4 (pH 6.8) buffer solution and cleaned up on a conditioned Bond-Elut cartridge. Tulathromycin, retained on the cartridge; it was eluted with methanol containing 2% formic acid, dried, re-constituted in methanol/1% formic acid, and analyzed by LC-MS. The limit of quantification (LOQ) of the method was 0.6 ng/mL in serum and 0.6 ng/g in tissue with RSDs ≤ 10% and accurate over the linear calibration range of 0.8-100 ng/mL for bison serum, 0.6-50 ng/mL for deer serum, 100-2500 ng/g for deer muscle tissue, and 500-5000 ng/g for deer lung tissue, all with coefficients of determination, r 2 ≥0.99. The validated method was used to quantify the concentration of tulathromycin residues in serum of bison and deer and selected tissue (lung and muscle tissue) samples obtained from 10 healthy, white-tailed deer that were administered the therapeutic dose approved for cattle (i.e., a single 2.5 mg/kg subcutaneous injection of tulathromycin in the neck). The deer were included in a tulathromycin drug depletion study.

Respiratory tract infections are common in farmed North American white-tailed deer (Odocoileus virginianus). Tulathromycin is approved for use in cattle but not deer but is often employed to treat deer. The pharmacokinetic properties and lung and muscle concentrations of tulathromycin in white-tailed deer were investigated. Tulathromycin was administered to 10 deer, and then, serum, lung, and muscle tulathromycin concentrations were measured using liquid chromatography-mass spectrometry (LC-MS). The mean maximal serum tulathromycin concentration in deer was 359 ng/mL at 1.3 h postinjection. The mean area under the serum concentration-time curve, apparent volume of distribution, apparent clearance, and half-life was 4883 ng·h/mL, 208 L/kg, 0.5 L/h/kg, and 281 h (11.7 days), respectively. The maximal tulathromycin concentration in lung and muscle homogenate from a single animal was 4657 ng/g (14 days) and 2264 ng/g (7 days), respectively. The minimum concentrations in lung and muscle were 39.4 ng/g (56 days) and 9.1 ng/g (56 days), respectively. Based on similarity in maximal serum concentrations between deer and cattle and high lung concentrations in deer, we suggest the recommended cattle dosage is effective in deer. Tissue concentrations persisted for 56 days, suggesting a need for longer withdrawal times in deer than cattle. Further tissue distribution and depletion studies are necessary to understand tulathromycin persistence in deer tissue; clinical efficacy studies are needed to confirm the appropriate dosage regimen in deer.

Tulathromycin is approved for the treatment of respiratory disease in cattle and swine. It is intended for long-acting, single-dose injection therapy (Draxxin), making it particularly desirable for use in bison due to the difficulty in handling and ease of creating stress in these animals. The pharmacokinetic properties of tulathromycin in bison were investigated. Ten wood bison received a single 2.5 mg/kg subcutaneous injection of Draxxin. Serum concentrations were measured by liquid chromatography-mass spectrometry (LC-MS) detection. Tulathromycin demonstrated early maximal serum concentrations, extensive distribution, and slow elimination characteristics. The mean maximum serum concentration (Cmax) was 195 ng/mL at 1.04 h (tmax) postinjection. The mean area under the serum concentration-time curve, extrapolated to infinity (AUC0-inf ), was 9341 ng · h/mL. The mean apparent volume of distribution (Vd /F) and clearance (Cls/F) was 111 L/kg and 0.4 L/h/kg, respectively, and the mean half-life (t1/2) was 214 h (8.9 days). Compared to values for cattle, Cmax and AUC0-inf were lower in bison, while the Vd /F was larger and the t1/2 longer. Tissue distribution and clinical efficacy studies in bison are needed to confirm the purported extensive distribution of tulathromycin into lung tissue and to determine whether a 2.5 mg/kg subcutaneous dosage is adequate for bison.