Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus) K. A. CLOTHIER* T. LEAVENS   R. W. GRIFFITH* S. E. WETZLICH à R. E. BAYNES   J. E. RIVIERE   & L. A. TELL à *Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA;   Food Animal Residue Avoidance Databank, Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA; à Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., Tell, L. A. Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus). J. vet. Pharmacol. Therap. 35, 113–120. Tulathromycin is a macrolide antimicrobial labeled for treatment of bacterial pneumonia in cattle and swine. The purpose of the present research was to evaluate tissue concentrations of tulathromycin in the caprine species. A tandem mass spectrometry regulatory analytical method that detects the common fragment of tulathromycin in cattle and swine was validated with goat tissues. The method was used to study tulathromycin depletion in goat tissues (liver, kidney, muscle, fat, injection site, and lung) over time. In two different studies, six juvenile and 25 market-age goats received a single injection of 2.5 mg ⁄ kg of tulathromycin subcutaneously; in a third study, 18 juvenile goats were treated with 2.5, 7.5, or 12.5 mg ⁄ kg tulathromycin weekly with three subcutaneous injections. Mean tulathromycin tissue concentrations were highest at injection site samples in all studies and all doses. Lung tissue concentrations were greatest at day 5 in market-age goats while in the multi-dose animals concentrations demonstrated dose-dependent increases. Concentrations were below limit of quantification in injection site and lung by day 18 and in liver, kidney, muscle, and fat at all time points. This study demonstrated that tissue levels in goats are very similar to those seen in swine and cattle. (Paper received 15 October 2010; accepted for publication 23 March 2011) Kristin A. Clothier, California Animal Health and Food Safety Lab, West Health Sciences Drive, College of Veterinary Medicine, University of California, Davis, CA 95616, USA. E-mail: clothier@cahfs.ucdavis.edu INTRODUCTION The Animal Medicinal Drug Use Clarification Act (AMDUCA) of 1994 (FDA, 1994) permits the use of certain approved animal and human drugs in an extralabel manner under a valid veterinary–client–patient relationship (Berge et al., 2006). Determination of appropriate withdrawal periods for this use is the responsibility of the prescribing veterinarian (Fajt, 2001, 2003; Berge et al., 2006). Extrapolation of data from other species to estimate drug behavior may increase the likelihood of violative drug residues in products for human consumption. Bacterial pneumonia is a frequent health problem in caprines, with Mannheimia haemolytica, Pasteurella multocida, and Myco- plasma spp. implicated as the most common bacterial causes (Brogden et al., 1998; Ackermann & Brogden, 2000; Zamri-Saad & Mera, 2001; Berge et al., 2006; Washburn et al., 2007; Yener et al., 2009). Ceftiofur is the only antimicrobial presently labeled in this species (Fajt, 2001, 2003; Webb et al., 2004; Washburn et al., 2007); however, cephalosporins have some limitations. For ceftiofur sodium, treatment of goats requires daily admin- istration, which may be difficult to accomplish under field conditions (Courtin et al., 1997). Concerns over cephalosporin resistance in human bacterial strains may lead to potential restrictions on their use in food animals (Nolen, 2009). Additionally, cephalosporins are not active against Mycoplasma species which are important pathogens of goats (Rosenbusch et al., 2005). Macrolide antibiotics rapidly disseminate from plasma to pulmonary parenchyma making them useful therapeutics against bacterial pneumonia (Williams & Sefton, 1993). Newer macrolides display enhanced lung penetration and extended tissue half lives (Benchaoui et al., 2004). Tulathromycin, a macrolide labeled to treat bacterial respiratory disease in cattle and swine, provides a seven day treatment with a single injection, indicating that it could be a useful therapeutic agent J. vet. Pharmacol. Therap. 35, 113–120. doi: 10.1111/j.1365-2885.2011.01300.x. Ó 2011 Blackwell Publishing Ltd 113