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Pharmacokinetics of florfenicol after intravenous administration in E scherichia coli lipopolysaccharide‐induced endotoxaemic sheep
Author(s) -
Pérez R.,
Palma C.,
Drápela C.,
Sepulveda M.,
Espinoza A.,
Peñailillo A. K.
Publication year - 2015
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12160
Subject(s) - pharmacokinetics , lipopolysaccharide , crossover study , florfenicol , pharmacology , bolus (digestion) , saline , intravenous bolus , chemistry , escherichia coli , antibiotics , medicine , placebo , biochemistry , alternative medicine , pathology , gene
Experiments in different animal species have shown that febrile conditions, induced by E scherichia coli lipopolysaccharide ( LPS ), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS ‐induced acute‐phase response ( APR ) model on plasma pharmacokinetics of florfenicol ( FFC ) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 ( LPS ) was treated with three intravenous doses of 1 μg/kg bw of E . coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution ( SS ) at similar intervals as LPS . At 24 h after the first injection of LPS or SS , an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann–Whitney U ‐test. The mean values of AUC 0–∞ in the endotoxaemic sheep (105.9 ± 14.3 μg·h/mL) were significantly higher ( P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 μg·h/mL). The total mean plasma clearance (CL T ) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS ‐treated sheep. A significant increase ( P < 0.05) in the terminal half‐life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E . coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the drug.