Pulmonary disposition of tilmicosin in foals and in vitro activity against Rhodococcus equi and other common equine bacterial pathogens

Abstract

The objectives of this study were to determine the serum and pulmonary disposition of tilmicosin in foals and to investigate the in vitro activity of the drug against Rhodococcus equi and other common bacterial pathogens of horses. A single dose of a new fatty acid salt formulation of tilmicosin (10 mg/kg of body weight) was administered to seven healthy 5- to 8-week-old foals by the intramuscular route. Concentrations of tilmicosin were measured in serum, lung tissue, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and blood neutrophils. Mean peak tilmicosin concentrations were significantly different between sampling sites with highest concentrations measured in blood neutrophils (66.01+/-15.97 microg/mL) followed by BAL cells (20.1+/-5.1 microg/mL), PELF (2.91+/-1.15 microg/mL), lung tissue (1.90+/-0.65 microg/mL), and serum (0.19+/-0.09 microg/mL). Harmonic mean terminal half-life in lung tissue (193.3 h) was significantly longer than that of PELF (73.3 h), bronchoalveolar cells (62.2 h), neutrophils (47.9 h), and serum (18.4 h). The MIC90 of 56 R. equi isolates was 32 microg/mL. Tilmicosin was active in vitro against most streptococci, Staphylococcus spp., Actinobacillus spp., and Pasteurella spp. The drug was not active against Enterococcus spp., Pseudomonas spp., and Enterobacteriaceae.

Kinetics and intrapulmonary disposition of tilmicosin after single and repeated oral bolus administrations to rabbits

“…negative bacteria that cause respiratory disease, such as Actinobacillus pleuropneumoniae, Pasteurella multocida, Mannhemia haemolityca, and Mycoplasma (Womble et al 2006). Clinical studies carried out in swine and calves by TIM oral administration have confirmed its good efficacy against pathogen pulmonary bacteria and its ability to modulate the inflammatory process by reducing inflammatory mediators in lung tissue (Scorneaux and Shryock 1998;Chin et al 1998).…”

Quantitative determination of tilmicosin in canine serum by high performance liquid chromatography–tandem mass spectrometry

“…The sample preparation and chromatographic separation combined with tandem mass spectrometric detection provide sufficient selectivity, minimize the effects of matrix on the results, and use a relatively small amount of sample compared to currently published methods [11][12][13][14][15].…”

“…A recent review [2] of analytical methods published in the past two decades for the determination of macrolide antimicrobials clearly emphasizes this point. While there were many methods that included the determination of tilmicosin in various tissues [3][4][5][6][7][8][9][10], only five methods were recognized for the quantitation of tilmicosin in plasma or serum [11][12][13][14][15]. Many methods that have been published for biological fluids utilize either liquid chromatography with UV detection or microbiological analysis, obtaining various limits of quantitation.…”

Antimicrobial drug concentrations and sampling techniques in the equine lung

“…BAL has also been described in horses in pulmonary pharmacokinetic studies for the recovery of PELF and/or AM for measuring drug concentrations. The majority of these studies were performed in foals, reporting intra-and extra-cellular drug concentrations after repeated sampling during 24 h post drug administration (Jacks et al, 2002;Womble et al, 2006aWomble et al, ,b, 2007Suarez-Mier et al, 2007;Venner et al, 2010). Other studies were performed in adult horses with or without a dilution marker for quantifying purposes Murray, 2000, 2004;Gardner et al, 2004;Art et al, 2007).…”