Pharmacokinetics of gamithromycin in pigs

Objectives : Gamithromycin, a 15-membered semi-synthetic macrolide antibiotic of the azalide subclass, has recently been developed for the treatment and prevention of bovine respiratory disease (BRD). Besides the anti-infectious properties, macrolides have frequently been reported to be able to influence various inflammatory processes, such as the production of pro-inflammatory cytokines and mediators. The aim of this study was to determine the pharmacokinetic (PK) parameters of gamithromycin in pigs, whereafter the disposition of the antibiotic can be used in further research to investigate its immunomodulating properties in a porcine lipopolysaccharide (LPS) inflammation model.Materials and Methods : Twelve male pigs, with a mean body weight (BW) of 24.4 kg were randomly divided in two groups. The animals received a single injection of 6 mg/kg BW gamithromycin (ZACTRAN®, Merial), either intravenously (IV) in the ear vein (n = 6) or subcutaneously (SC) (n = 6). Blood was collected from the jugular vein into EDTA tubes before administration; on day 0 at 15, 30 and 45 minutes and 1, 2, 4, 6, 8, 10, 12 and 24 h post administration (p.a.) and once daily from day 2 to day 14 p.a. (24 h intervals). Plasma was isolated and stored at ≤ -15°C until analysis. Quantitation of gamithromycin in the plasma samples was performed using an in-house developed and validated LC-MS/MS method. The pharmacokinetic parameters were analyzed using the software program WinNonlin (Pharsight).Results and Conclusions : The area under the plasma concentration-time curve (AUC0→∞), absolute bioavailability (F), half-life of absorption and elimination (t1/2abs and t1/2el, respectively), volume of distribution (Vd), clearance (Cl), maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined and critically compared to the PK parameters in cattle and foals1,2.Results and conclusions will be presented at the congress.References1. Huang et al., 2010, J. vet. Pharmacol. Therap. 33(3), 227-2372. Berghaus et al., 2012, J. vet. Pharmacol. Therap. 35(1), 59-66Objectives : Gamithromycin, a 15-membered semi-synthetic macrolide antibiotic of the azalide subclass, has recently been developed for the treatment and prevention of bovine respiratory disease (BRD). Besides the anti-infectious properties, macrolides have frequently been reported to be able to influence various inflammatory processes, such as the production of pro-inflammatory cytokines and mediators. The aim of this study was to determine the pharmacokinetic (PK) parameters of gamithromycin in pigs, whereafter the disposition of the antibiotic can be used in further research to investigate its immunomodulating properties in a porcine lipopolysaccharide (LPS) inflammation model.Materials and Methods : Twelve male pigs, with a mean body weight (BW) of 24.4 kg were randomly divided in two groups. The animals received a single injection of 6 mg/kg BW gamithromycin (ZACTRAN®, Merial), either intravenously (IV) in the ear vein (n = 6) or subcutaneously (SC) (n = 6). Blood was collected from the jugular vein into EDTA tubes before administration; on day 0 at 15, 30 and 45 minutes and 1, 2, 4, 6, 8, 10, 12 and 24 h post administration (p.a.) and once daily from day 2 to day 14 p.a. (24 h intervals). Plasma was isolated and stored at ≤ -15°C until analysis. Quantitation of gamithromycin in the plasma samples was performed using an in-house developed and validated LC-MS/MS method. The pharmacokinetic parameters were analyzed using the software program WinNonlin (Pharsight).Results and Conclusions : The area under the plasma concentration-time curve (AUC0→∞), absolute bioavailability (F), half-life of absorption and elimination (t1/2abs and t1/2el, respectively), volume of distribution (Vd), clearance (Cl), maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined and critically compared to the PK parameters in cattle and foals1,2.Results and conclusions will be presented at the congress.References1. Huang et al., 2010, J. vet. Pharmacol. Therap. 33(3), 227-2372. Berghaus et al., 2012, J. vet. Pharmacol. Therap. 35(1), 59-66C