title: Pharmacokinetics of tulathromycin in healthy and neutropenic mice challenged intranasally with lipopolysaccharide from Escherichia coli.
abstract: Tulathromycin represents the first member of a novel subclass of macrolides, known as triamilides, approved to treat bovine and swine respiratory disease. The objectives of the present study were to assess the concentration-versus-time profile of tulathromycin in the plasma and lung tissue of healthy and neutropenic mice challenged intranasally with lipopolysaccharide (LPS) from Escherichia coli O111:B4. BALB/c mice were randomly allocated into four groups of 40 mice each: groups T-28 (tulathromycin at 28 mg/kg of body weight), T-7, T7-LPS, and T7-LPS-CP (cyclophosphamide). Mice in group T-28 were treated with tulathromycin at 28 mg/kg subcutaneously (s.c.) (time 0 h). The rest of the mice were treated with tulathromycin at 7 mg/kg s.c. (time 0 h). Animals in dose groups T-7-LPS and T7-LPS-CP received a single dose of E. coli LPS intranasally at -7 h. Mice in group T7-LPS-CP were also rendered neutropenic with cyclophosphamide (150 mg/kg intraperitoneally) prior to the administration of tulathromycin. Blood and lung tissue samples were obtained from 5 mice from each dose group at each sampling time over 144 h after the administration of tulathromycin. There were not statistical differences in lung tissue concentrations among groups T-7, T-7-LPS, and T7-LPS-CP. For all dose groups, the distribution of tulathromycin in the lungs was rapid and persisted at relatively high levels during 6 days postadministration. The concentration-versus-time profile of tulathromycin in lung tissue was not influenced by the intranasal administration of E. coli LPS. The results suggest that in mice, neutrophils may not have a positive influence on tulathromycin accumulation in lung tissue when the drug is administered during either a neutrophilic or a neutropenic state.
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA.
authors.forename: N
authors.initials: N
authors.lastname: Villarino
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: T
authors.initials: T
authors.lastname: Martín-Jiménez
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004187:Disaccharides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004926:Escherichia coli; D005260:Female; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia; D009504:Neutrophils; D011897:Random Allocation; D018942:Macrolides
chemical_list: D000900:Anti-Bacterial Agents; D004187:Disaccharides; D006571:Heterocyclic Compounds; D008070:Lipopolysaccharides; C485204:tulathromycin; D018942:Macrolides