Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus)

Abstract

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.

Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats

“…Recently, the pharmacokinetics of tulathromycin has been studied in both juvenile and market goats (Young et al. , 2011; Clothier et al. , in press a, in press b).…”

Pharmacokinetics of tulathromycin in edible tissues of healthy and experimentally infected pigs withActinobacillus pleuropneumoniae

“…Those studies were performed mainly with healthy animals and most of them were focused on the pharmacokinetics in lung tissue, as a target organ Nowakowski et al 2004;Cox et al 2010;Villarino et al 2012;Villarino et al 2013bVillarino et al , 2013c. So far, only a few studies deals with the determination of tulathromycin in muscle and other edible tissues of pigs, cattle or goats (EMEA 2004;Boner and Gottschall 2011;Clothier et al 2012;Romanet et al 2012). According to the EMA report the residue A c c e p t e d M a n u s c r i p t concentrations of tulathromycin in the pig liver were 1700, 960, 730, 280 and 150 μg kg -1 on days 5, 12, 18, 25 and 36 after treatment.…”

Caprine Abscess Model of Tulathromycin Concentrations in Interstitial Fluid from Tissue Chambers Inoculated with Corynebacterium pseudotuberculosis following Subcutaneous or Intrachamber Administration

“…To date, none of the studies using systemic or intralesion antimicrobials for CL has described drug concentrations within lesions or demonstrated whether tulathromycin retains antimicrobial activity in vivo in abscessed purulent material. The pharmacokinetics of this drug in goats have been recently described (11,12). The antimicrobial susceptibility of C. pseudotuberculosis to tulathromycin has not been reported, although we found that the MIC 90 of 35 clinical case-derived isolates was 2 g/ml, and 71% of these isolates had an MIC of Ͻ1 g/ml (K. E. Washburn, M. Libal, unpublished data).…”