Pharmacokinetics of tulathromycin and its metabolite in swine administered with an intravenous bolus injection and a single gavage

Abstract

Tulathromycin is a macrolide antimicrobial agent proposed for therapeutic use in treatment of porcine and bovine respiratory disease. In this study, the absolute bioavailability of tulathromycin solution was investigated in pigs. Eight pigs, with body weight of 20.5 ± 1.6 kg, were given a single dose of tulathromycin at 2.5 mg/kg oral (p.o.) and intravenous (i.v.) in a crossover design. The plasma concentrations of tulathromycin and its metabolite were determined by LC-MS/MS method, and the pharmacokinetic parameters of tulathromycin were calculated by noncompartmental analysis. After p.o. administration, the maximum plasma concentration (C(max) ) was 0.20 ± 0.05 μg/mL at 3.75 ± 0.71 h. The terminal half-life (t(1/2λz) ) in plasma was 78.7 ± 6.75 h, and plasma clearance (Cl/F) was 1.14 ± 0.28 L/h/kg. After i.v. injection, plasma clearance (Cl) was 0.580 ± 0.170 L/h/kg, the volume of distribution (Vz) was 64.3 ± 21.2 L/kg, and the t(1/2λz) was 76.5 ± 13.4 h. In conclusion, an analytical method for the quantification of tulathromycin and its metabolite in plasma in swine was developed and validated. Following p.o. administration to pigs at 2.5 mg/kg b.w., tulathromycin was rapidly absorbed and the systemic bioavailability was 51.1 ± 10.2.

Pharmacokinetic/Pharmacodynamic Modeling of Tulathromycin against Pasteurella multocida in a Porcine Tissue Cage Model

“…Pharmacokinetic studies of tulathromycin have been conducted in various species, including pigs (Wang et al, 2012; Villarino et al, 2013; Gajda et al, 2016). However, there have been no studies that applied PK and ex vivo PD principles to evaluate the antibacterial effects of tulathromycin in piglets.…”

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.…”

“…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

“…administration. In contrast, oral administration of tulathromycin, using a compounded formulation, had a lower systemic availability (~50%; Wang et al, 2012). In plasma, tulathromycin has a long terminal half-life, ranging across species from~2 to~5 days except in mice in which the terminal half-life is <20 h ( Table 1).…”