Pulmonary pharmacokinetics of tulathromycin in swine. Part 2: Intra‐airways compartments

Abstract

The objective of this study was to assess the pharmacokinetics of tulathromycin in pulmonary and bronchial epithelial lining fluid (PELF and BELF) from pigs. Clinically healthy pigs were allocated to two groups of 36 animals each. All animals were treated with tulathromycin (2.5 mg/kg/i.m). Animals in group 2 were also challenged intratracheally with lipopolysaccharide from Escherichia coli 3 h prior to tulathromycin administration. Both PELF and BELF samples were harvested using bronchoalveolar lavage fluid and bronchial micro-sampling probes, respectively. Samples were taken for 17 days post-tulathromycin administration. No statistical differences in the concentration of tulathromycin were observed in PELF between groups. The concentration vs. time profile in BELF was evaluated only in Group 1. Tulathromycin distributed rapidly and extensively into the airway compartments. The time to maximal (Tmax ) concentration was 6 h postdrug administration in PELF but 72 h post-tulathromycin administration for BELF. In group 2, the Tmax was seen at 24 h post-tulathromycin administration. The area under the concentration time curve (h*ng/mL) was 522 000, 348 000 and 1 290 000 for PELFGroup-1 , PELFGroup-2 , and BELFGroup-1 , respectively. Tulathromycin not only distributed rapidly into intra-airway compartments at relatively high concentrations but also resided in the airway lining fluid for a long time (>4 days).

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

“…The pharmacokinetic properties of tulathromycin have been studied in mice (Villarino et al 2012), cattle Cox et al 2010), pigs Wang et al, 2012;Villarino et al 2013bVillarino et al , 2013c, goats (Clothier et al 2011;Young et al 2011) and foals (Venner et al 2010). 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.…”

“…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).…”

“…Therefore, it is reasonable to expect that the influence of the inflammatory response on the tissue kinetics of a drug will be change with time (Villarino et al 2013b). Although some studies have been published regarding pharmacokinetics of tulathromycin in food producing animals Nowakowski et al 2004;Cox et al 2010;Clothier et al 2011;Young et al 2011;Romanet et al 2012;Wang et al 2012;Villarino et al 2013bVillarino et al , 2013cGrismer et al The therapeutic use of tulathromycin in food producing animals must be assessed not only in terms of good clinical efficacy but also considering the risk of the presence of residues in edible tissues. There is a strict legislative framework controlling the use of antibiotics, with the aim of minimizing the risk to human health associated with consumption of their residues.…”

Understanding the pharmacokinetics of tulathromycin: a pulmonary perspective

“…Lung pharmacokinetic studies in cattle, pigs, horses, and mice show that tulathromycin accumulates in lung tissue (Fig. ; Benchaoui et al ., ; Nowakowski et al ., ; Cox et al ., ; Venner et al ., ; Young et al ., ; Villarino et al ., ,b). Within the lung, the drug may be sequestered in cells compartments (lysosomes), bounded to proteins (e.g., mucus in the airways), and free in the interstitium.…”

“…Least squares mean concentration (+ 2 SE ) of tulathromycin in LT (ng/g), PELF (ng/ mL ), and BELF (ng/ mL ) and mean concentration (+ 2 SE ) in plasma (ng/ mL ) from pigs administered a single i.m. injection of tulathromycin at 2.5 mg/kg body weight (adapted from Villarino et al ., ,b). …”