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

摘要

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 mu g/mL at 3.75 +/- 0.71 h. The terminal half-life (t(1/2 lambda z)) 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(1/2 lambda z) 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.