Pharmacokinetics and lung tissue concentrations of tulathromycin in swine

Abstract

The absolute bioavailability and lung tissue distribution of the triamilide antimicrobial, tulathromycin, were investigated in swine. Fifty-six pigs received 2.5 mg/kg of tulathromycin 10% formulation by either intramuscular (i.m.) or intravenous (i.v.) route in two studies: study A (10 pigs, i.m. and 10 pigs, i.v.) and study B (36 pigs, i.m.). After i.m. administration the mean maximum plasma concentration (C(max)) was 616 ng/mL, which was reached by 0.25 h postinjection (t(max)). The mean apparent elimination half-life (t(1/2)) in plasma was 75.6 h. After i.v. injection plasma clearance (Cl) was 181 mL/kg.h, the volume of distribution at steady-state (V(ss)) was 13.2 L/kg and the elimination t(1/2) was 67.5 h. The systemic bioavailability following i.m. administration was >87% and the ratio of lung drug concentration for i.m. vs. i.v. injection was > or =0.96. Following i.m. administration, a mean tulathromycin concentration of 2840 ng/g was detected in lung tissue at 12 h postdosing. The mean lung C(max) of 3470 ng/g was reached by 24 h postdose (t(max)). Mean lung drug concentrations after 6 and 10 days were 1700 and 1240 ng/g, respectively. The AUC(inf) was 61.4 times greater for the lung than for plasma. The apparent elimination t(1/2) for tulathromycin in the lung was 142 h (6 days). Following i.m. administration to pigs at 2.5 mg/kg body weight, tulathromycin was rapidly absorbed and highly bioavailable. The high distribution to lung and slow elimination following a single dose of tulathromycin, are desirable pharmacokinetic attributes for an antimicrobial drug indicated for the treatment of respiratory disease in swine.

A single laboratory‐validated LC‐MS method for the analysis of tulathromycin residues in bison and deer sera and selected tissues of white‐tailed deer

“…Application of the method for the analysis of incurred tulathromycin residues in bison serum, deer serum, and selected tissues The bison were administered a single 2.5 mg/kg body weight (bw) subcutaneous (SC) injection of Draxxin (Zoetis Canada, Kirkland, QC, Canada) in the lateral neck. Blood samples were collected in 10 mL serum vacutainer tubes by jugular venipuncture preinjection at 0, 1, 2, 4, 12 hours, and 1, 1.5, 2, 3, 4, 5,6,7,8,9,10,11,13,15,17,19,21,23, and 25 days post-injection. Serum was separated from blood samples by centrifugation (Eppendorf 5804 R Centrifuge) at 1500 x g for 10 min, transferred to micro-centrifuge tubes, and stored at À80°C until analysis.…”

“…[1][2][3][4] Tulathromycin, with a molecular formula of C 41 H 79 N 3 O 12 and molecular mass of 806.23 ( Figure 1), is a semi-synthetic macrolide antibiotic approved to treat bovine and swine bacterial respiratory disease but not for white-tailed deer or bison. [5][6][7][8][9] It is also used as a preventative measure in cattle feedlots to reduce the risk of contracting respiratory disease, such as those pathogens associated with Pasteurella, Mannheimia, Actinobacillusm, and Mycoplasma species. [5,6,8] The commercial product, Draxxin, is formulated as a long-acting, single-dose injection therapy.…”

“…[5,6,8] The commercial product, Draxxin, is formulated as a long-acting, single-dose injection therapy. [5,6,9] In an aqueous solution, tulathromycin equilibrates into a stable mixture of two isomers, tulathromycin A (CP-472,295, a 15-ring member) and tulathromycin B (CP-547,272, a 13-ring member) in a 9:1 ratio, respectively. [5][6][7] The chemical structure of the compound consists of three polar amine groups, which allows for greater penetration into tissues and continued activity in the lung after a single injection.…”

“…[5][6][7] The chemical structure of the compound consists of three polar amine groups, which allows for greater penetration into tissues and continued activity in the lung after a single injection. [6,[8][9][10][11] These desirable characteristics have promoted the off-label use of tulathromycin in white-tailed deer where multiple handling by people is difficult and pose significant injury risk and stress to these animals even though the drug is not specifically approved for use in these species. These same characteristics are also desirable in the bison industry where the difficulty associated with bison handling is a critical barrier to effective therapy.…”

“…Liquid chromatography coupled to mass spectrometry (LC-MS) has become standard practice in pharmacokinetic analysis for the analysis of drugs in food and biological samples due to its excellent sensitively and selectivity and the ability to quantify drugs at trace levels. [12][13][14][15][16] LC-MS methods have been reported for tulathromycin in plasma and tissue samples in cattle, [9,10,15] swine, [9,17,18] goats, [19][20][21] and foals. [22,23] There were, however, no reported methods for the determination of pharmacokinetic parameters in either the bison or the white-tailed deer.…”