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Gamithromycin is a new macrolide antibiotic that is only registered for use in cattle to treat respiratory disorders such as bovine respiratory disease. The aim of this study was to determine the pharmacokinetics of gamithromycin in broiler chickens. Gamithromycin (6 mg/kg of BW) was injected intravenously (IV) or subcutaneously (SC) to six 4-wk-old chickens in a parallel study design, and blood was collected at different time points postadministration. Quantification of gamithromycin in plasma was performed using an in-house validated liquid chromatography-tandem mass spectrometry method and the pharmacokinetics analyzed according to a 2-compartmental model. Following IV administration, the mean area under the plasma concentration-time curve (AUC0→∞), and α and β half-life of elimination (t1/2el α and t1/2el β) were 3,998 h•ng/mL, 0.90 h, and 14.12 h, respectively. Similar values were obtained after a SC bolus injection, i.e., 4,095 h•ng/mL, 0.34 h, and 11.63 h, for AUC0→∞, t1/2el α, and t1/2el β, respectively. The mean maximum plasma concentration (889.46 ng/mL) appeared at 0.13 h. Gamithromycin showed a large volume of distribution after IV as well as SC administration, 27.08 and 20.89 L/kg, respectively, and a total body clearance of 1.61 and 1.77 L/h•kg, respectively. The absolute bioavailability was 102.4%, showing that there is a complete absorption of gamithromycin after a SC bolus injection of 6 mg/kg of BW.

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The macrolide gamithromycin (GAM) has the ability to accumulate in tissues of the respiratory tract. Consequently, GAM might be a suitable antibiotic to treat bacterial respiratory infections in poultry, such as Ornithobacterium rhinotracheale. As O. rhinotracheale infections are common in turkey flocks, the aim of this study was to determine the pharmacokinetic (PK) parameters of GAM in plasma, lung tissue, and pulmonary epithelial lining fluid (PELF) of turkeys and to correlate them with pharmacodynamic (PD) characteristics (PK/PD). The animal experiment was performed with 64 turkeys, which received either a subcutaneous (SC, n=32) or an oral (PO, n=32) bolus of 6 mg GAM/kg body weight (BW). GAM concentrations in plasma, lung tissue, and PELF were measured at different time points post administration (p.a.), and PK characteristics were determined using non-compartmental modeling. The maximum plasma concentration after PO administration was ten-fold lower than after SC injection (0.087 and 0.89 μg/mL, respectively), whereas there was no difference in lung concentrations between both routes of administration. However, lung concentrations at day 1 p.a. were significantly higher than plasma levels for both routes of administration (2.22 and 3.66 μg/g for PO and SC, respectively). Consequently, lung/plasma ratios were high, up to 50 and 80 after PO and SC administration, respectively. GAM could not be detected in PELF, although this might be attributed to the collection method of PELF in birds. The GAM minimum inhibitory concentration (MIC) was determined for 38 O. rhinotracheale strains; MIC50 and MIC90 were 2 and >32 μg/mL, respectively. PK/PD correlation for lung tissue demonstrated that the time above the MIC90 of the susceptible population (2 μg/mL) was 1 day after PO bolus and 3.5 days after SC administration. The area under the curve (AUClast)/MIC ratios for lung tissue after SC and PO administration were 233 and 90, respectively. To conclude, GAM is highly distributed to lung tissue in turkey poults, suggesting that it has the potential to be used to treat respiratory infections such as O. rhinotracheale.

a b s t r a c tThe pharmacokinetics of dexamethasone (DEX) were investigated after an intravenous (IV) or intramuscular (IM) bolus injection of 0.3 mg/kg bodyweight DEX sodium phosphate in pigs. The plasma concentrations of DEX were determined using a validated high-performance liquid chromatographytandem mass spectrometry (LC-MS/MS) method and the pharmacokinetics were determined by one-compartmental analysis.The mean area under the plasma concentration-time curve and the mean elimination half-life were 133.07 ± 39.59 ng.h/mL and 0.77 h, and 173.24 ± 53.59 ng h/mL and 1.06 h following IV and IM administration, respectively. The volume of distribution and clearance recorded after IV administration were 2.78 ± 0.88 L/kg and 2.39 ± 0.57 L/h kg, respectively.An IM bolus injection of DEX sodium phosphate in pigs resulted in a fast and complete absorption, with a mean maximal plasma concentration of 80.94 ± 21.29 ng/mL at 0.35 ± 0.21 h and a high absolute bioavailability of 131.06 ± 26.05%.Ó 2013 Elsevier Ltd. All rights reserved.Dexamethasone (DEX) is a long-acting synthetic hydrocortisone analogue and is one of the most potent glucocorticoid drugs. It is extensively used in veterinary medicine to treat inflammatory, immunological and allergic disorders (Toutain et al., 1982; EMA, 2004;Ferguson et al., 2009). In livestock, the use of DEX is indicated in inflammatory processes such as mastitis, aseptic laminitis, arthritis and primary ketosis. DEX is also reported to be used as an illegal growth promoter (Courtheyn et al., 2002;Ferguson et al., 2009;Vincenti et al., 2009).In order to improve water solubility, glucocorticoids are often formulated as a phosphate ester prodrug, which rapidly hydrolyses and releases free and active alcohols (Rohdewald et al., 1987; EMA, 2004). The pharmacokinetic (PK) properties of DEX have been previously described in humans and diverse animal species, but not in pigs although it has been approved for treatment of inflammatory and allergic disorders in this species (EMA, 2004).The aim of this study was to determine the PK properties of DEX in pigs. The results will be applied in ongoing research studying the immunomodulatory properties of DEX, either alone or in combination with several antibiotics in a porcine lipopolysaccharide (LPS) inflammation model .The experiment was approved by the Ethical Committee of the Faculty of Veterinary Medicine of Ghent University (EC 2011/156).Six clinically healthy male pigs (Landrace) with a mean bodyweight (BW) of 28.3 ± 3.01 kg were randomly divided in two groups. The animals had free access to feed and drinking water. The experiment was performed as a two-way cross-over design with a wash-out period of 5 days. A bolus of 0.3 mg/kg BW DEX sodium phosphate (DEXA 0.2%, Kela Laboratoria) was injected intravenously (IV) in the ear vein or intramuscularly (IM) in the gluteus muscle via a sterile winged infusion needle (25 G; Micro-flo, Novolab). Blood was collected by venepuncture of the jugular vein into EDTA-coated tubes (Vacutest Kima) before admin...

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