title: Pharmacokinetic and pharmacodynamic properties of gamithromycin in turkey poults with respect to Ornithobacterium rhinotracheale.
abstract: 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.
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry Anneleen.Watteyn@UGent.be.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Watteyn
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry.
authors.forename: Mathias
authors.initials: M
authors.lastname: Devreese
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry.
authors.forename: Siegrid
authors.initials: S
authors.lastname: De Baere
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry.
authors.forename: Heidi
authors.initials: H
authors.lastname: Wyns
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry.
authors.forename: Elke
authors.initials: E
authors.lastname: Plessers
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Boyen
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry.
authors.forename: Patrick
authors.initials: P
authors.lastname: De Backer
authors.affiliation: Department of Pharmacology, Toxicology and Biochemistry.
authors.forename: Siska
authors.initials: S
authors.lastname: Croubels
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D005260:Female; D045826:Flavobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D008168:Lung / Q000382:microbiology; D018942:Macrolides / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D045246:Ornithobacterium / Q000187:drug effects*; D011201:Poultry Diseases / Q000188:drug therapy* / Q000382:microbiology; D011897:Random Allocation; D014422:Turkeys
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C552399:gamithromycin
keywords: Ornithobacterium rhinotracheale; gamithromycin; pharmacodynamic; pharmacokinetic; turkey poult