Pharmacokinetics and tissue withdrawal study of tulathromycin in North American bison (Bison bison) and white-tailed deer (Odocoileus virginianus) using liquid chromatography-mass spectrometry
Tulathromycin is a macrolide antibiotic approved for use in cattle and swine respiratory disease. Extra-label use of tulathromycin occurs in bison and deer and significant interspecies differences in pharmacokinetics warrant specific investigation in these species. This study involved investigation of the pharmacokinetics of tulathromycin in bison and white-tailed deer following a single 2.5 mg/kg bw subcutaneous injection (n=10) of Draxxin (Pfizer Inc.) to provide important information regarding tulathromycin dosage regimens in these species. As well, tulathromycin distribution and depletion in deer muscle and lung tissues following a 2.5 mg/kg bw subcutaneous injection of Draxxin was investigated to obtain pilot information regarding withdrawal time of tulathromycin in deer. For the pharmacokinetic studies, serial blood samples were collected at baseline and up to 25 days post-injection. Pharmacokinetic parameters were estimated using non-compartmental methods. For the tissue pilot study, deer (n = 2 to 3) were slaughtered at 0, 1, 2, 6, 7, and 8 weeks post-injection. A quantitative analytical liquid chromatography-mass spectrometry method for measuring tulathromycin was developed and validated in bison and deer serum and deer lung and muscle according to international guidelines. Samples were processed by solid-phase extraction. Reverse-phase chromatography was performed by gradient elution. Positive electrospray ionization was used to detect the double charged ion [M+2H]+2 at m/z 403.9 and monitored in selected ion monitoring mode. Tulathromycin demonstrated early maximal serum concentrations, extensive distribution, and slow elimination characteristics in deer and bison. In bison, mean Cmax (195 ng/mL) was lower compared to cattle (300 to 500 ng/mL) and half-life (214 hours) longer (cattle, 90 to 110 hours). In deer, mean Cmax (359 ng/mL) is comparable to cattle, but half-life (281 hours) was much longer. Tissue distribution and clinical efficacy studies are needed in bison to confirm extensive distribution of tulathromycin into lung and the appropriate dosage regimen. Tulathromycin was extensively distributed to deer lung and muscle, with tissue levels peaking within 7 to 14 days after injection. Drug tissue concentrations were detected 56 days after treatment, longer than the established withdrawal time of 44 days in cattle. This prolonged drug concentration in the tissue is supportive for the administration of tulathromycin as a single injection therapy for treatment of respiratory disease of deer. While more study is needed to establish a recommended withdrawal time, the long serum and tissue drug half-life and extensive interindividual variability in tissue levels suggests a withdrawal period well beyond 56 days may be required in deer.
DegreeMaster of Science (M.Sc.)
DepartmentPharmacy and Nutrition
SupervisorAlcorn, Jane; Woodbury, Murray
CommitteeBoison, Joe; Chicoine, Al; El-Aneed, Anas
Copyright DateFebruary 2014
Pharmacokinetics, withdrawal, tulathromycin, liquid chromatography-mass spectrometry, bison, white-tailed deer