RESUMO
Fourier Transform infrared imaging and multivariate analysis were used to identify, at the microscopic level, the presence of florfenicol (FF), a heavily-used antibiotic in the salmon industry, supplied to fishes in feed pellets for the treatment of salmonid rickettsial septicemia (SRS). The FF distribution was evaluated using Principal Component Analysis (PCA) and Augmented Multivariate Curve Resolution with Alternating Least Squares (augmented MCR-ALS) on the spectra obtained from images with pixel sizes of 6.25⯵mâ¯×â¯6.25⯵m and 1.56⯵mâ¯×â¯1.56⯵m, in different zones of feed pellets. Since the concentration of the drug was 3.44â¯mg FF/g pellet, this is the first report showing the powerful ability of the used of spectroscopic techniques and multivariate analysis, especially the augmented MCR-ALS, to describe the FF distribution in both the surface and inner parts of feed pellets at low concentration, in a complex matrix and at the microscopic level. The results allow monitoring the incorporation of the drug into the feed pellets.
Assuntos
Salmão/metabolismo , Tianfenicol/análogos & derivados , Animais , Análise dos Mínimos Quadrados , Análise Multivariada , Análise de Componente Principal/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tianfenicol/metabolismoRESUMO
The aim of this study was to determine the effect of Escherichia coli lipopolysaccharide (LPS)-induced acute phase response (APR) on the pharmaco-kinetics and biotransformation of florfenicol (FFC) in rabbits. Six rabbits (3.0 ± 0.08 kg body weight (bw)) were distributed through a crossover design with 4 weeks of washout period. Pairs of rabbits similar in bw and sex were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 µg/kg bw of E. coli LPS at intervals of 6 h, and Group 2 (control) was treated with an equivalent volume of saline solution (SS) at the same intervals and frequency of Group 1. 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 were collected from the auricular vein before drug administration and at different times between 0.05 and 24.0 h after treatment. FFC and florfenicol-amine (FFC-a) were extracted from the plasma, and their concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using the paired Student t-test. The mean values of AUC0-∞ in the endotoxaemic rabbits (26.3 ± 2.7 µg·h/mL) were significantly higher (P < 0.05) than values observed in healthy rabbits (17.2 ± 0.97 µg·h/mL). The total mean plasma clearance (CLT ) decreased from 1228 ± 107.5 mL·h/kg in the control group to 806.4 ± 91.4 mL·h/kg in the LPS-treated rabbits. A significant increase (P < 0.05) in the half-life of elimination was observed in the endotoxaemic rabbits (5.59 ± 1.14 h) compared to the values observed in healthy animals (3.44 ± 0.57 h). In conclusion, the administration of repeated doses of 1 µg/kg E. coli LPS induced an APR in rabbits, producing significant modifications in plasma concentrations of FFC leading to increases in the AUC, terminal half-life and mean residence time (MRT), but a significant decrease in CLT of the drug. As a consequence of the APR induced by LPS, there was a reduction in the metabolic conversion of FFC to their metabolite FFC-a in the liver, suggesting that the mediators released during the APR induced significant inhibitory effects on the hepatic drug-metabolizing enzymes.
Assuntos
Antibacterianos/farmacocinética , Escherichia coli , Lipopolissacarídeos/toxicidade , Tianfenicol/análogos & derivados , Reação de Fase Aguda , Animais , Antibacterianos/sangue , Antibacterianos/metabolismo , Área Sob a Curva , Feminino , Meia-Vida , Masculino , Coelhos , Tianfenicol/sangue , Tianfenicol/metabolismo , Tianfenicol/farmacocinéticaRESUMO
Säo apresentados os resultados terapêuticos obtidos no tratamento de 34 pacientes portadores de donovanose, atendidos na Clínica Dermatológica da Universidade Federal de Pernambuco, Os pacientes foram tratados com tianfenicol na seguinte posologia: 2,5g sob forma de granulado, no primeiro dia e, a seguir, 500 mg de 12/12 horas até o desaparecimento das lesöes e a negativaçäo bacteriológica. Esta foi obtida em 82,4% dos pacientes a partir da segunda semana e em 100% na terceira semana de tratamento. Näo foram observados efeitos colaterais significativos ou intolerância a droga