title: Plasma and tissue disposition of florfenicol in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep.
abstract: 1. The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations. 2. Ten Suffolk Down sheep, 60.5 ± 4.7 kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1 μg/kg bw of LPS at 24, 16, and 0.75 h (45 min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20 mg FFC/kg was administered at 0.75 h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration. 3. The plasma AUC0-4 hvalues of FFC were higher (p = 0.0313) in sheep treated with LPS (21.8 ± 2.0 μg·min/mL) compared with the control group (12.8 ± 2.3 μg·min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (Cmax= 0.14 ± 0.01 μg/mL) with a metabolite ratio (MR) of 4.0 ± 0.87%. While in the LPS group, Cmaxincreased slightly (0.25 ± 0.01 μg/mL), and MR decreased to 2.8 ± 0.17%. 4. The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug.
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: Rubén
authors.initials: R
authors.lastname: Pérez-Fernández
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: Victoria
authors.initials: V
authors.lastname: Cazanga
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: Jessie Ana
authors.initials: JA
authors.lastname: Jeldres
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: Pedro P
authors.initials: PP
authors.lastname: Silva
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: José
authors.initials: J
authors.lastname: Riquelme
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: Fernando
authors.initials: F
authors.lastname: Quiroz
authors.affiliation: a Laboratorio de Farmacología , Departamento de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad de Concepción , Chillán , Chile and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Palma
authors.affiliation: b Instituto de Farmacología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile , Valdivia , Chile.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Carretta
authors.affiliation: b Instituto de Farmacología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile , Valdivia , Chile.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Burgos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism / Q000662:veterinary*; D004926:Escherichia coli; D008070:Lipopolysaccharides; D012756:Sheep / Q000378:metabolism* / Q000382:microbiology; D013839:Thiamphenicol / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; C035534:florfenicol; D013839:Thiamphenicol
keywords: Endotoxemia; florfenicol; lipopolysaccharide; sheep; tissues