Title: Pharmacokinetic and pharmacodynamic evaluations of levofloxacin in broiler chickens Objective: To evaluate the PK/PD and residues of levofloxacin (L) after IV and oral administrations in broiler chickens. Materials & Methods: 65 healthy broiler chickens were randomly divided into 4 groups (A n=20, B n=20, C n=20 and D n=5). Groups A, B and C received 5 mg/kg of L (A and B oral, C IV) while D was the control group. Blood samples were withdrawn at different scheduled times for the group A and C, while animals in group B were sub-divided in to 5 sub-groups (n=4) and euthanized for organ (liver, kidney, muscle, lung) collections at different times (1, 6, 10, 24, 48 h). L concentrations in blood and tissues were quantified by validated HPLC-FL method. PK data of L was fitted using a non-compartment model. As PD studies, two field E. coli isolates were collected from cloacal swabs. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against E.coli (isolated in clinical broilers) were determined in broth and in serum obtained from the healthy animals using the microdilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. In vitro and ex vivo anti-bacterial effects of L were determined using time killing curve. Solutions of L in serum (0.0, 0.03, 0.06, 0.125, 0.25, 0.5 and 1 μg/ml) and serum samples (10, 30 min, 1, 4, 6, 10, 24 and 48 h) were used for the determination of in vitro and ex vivo antibacterial effects against E. coli. In vivo Cmax/MIC and AUC24h/MIC, were calculated by linking PK data with PD index (MIC) for serum after oral administration of L in clinically isolated E. coli. Ex vivo AUC24h/MIC were obtained after 24h incubation from ex vivo time killing curve and fitted using the sigmoidal inhibitory Emax model. Using PK-PD modelling, the optimal oral dose in broilers were predicted. Results & Conclusion: The pharmacokinetic profiles of L after oral and IV administrations were almost overlapping in the elimination phase. The oral F% was 124±39. All the tested organs contained quantifiable L concentrations up to 48 hours. The liver was the most contaminated organ then in descending order kidney, lung and muscle. The results of ex vivo growth inhibition curves were consistent with the in vitro time-kill study. Plasma concentration above 8xMIC led to eradication of E.coli. The MIC and MBC of L in MHB and serum were 0.03, 0.06 and 0.125 μg/mL, respectively. The pharmacokinetic profiles of levofloxacin were similar with those in previous studies in chickens and calves. Levofloxacin showed plasma concentration dependent antibacterial activities against clinical E.coli. A dose of 5 mg/kg of L appears to be able to kill E.coli. Keywords: broiler chickens, levofloxacin, pharmacokinetics, pharmacodynamics, residues References: 1. Giorgi, M., Rota, S., Giorgi, T., Capasso, M., Briganti, A., 2013. Journal of Exotic Pet Medicine 22, 192-199.
Pharmacokinetic and pharmacodynamic evaluations of levofloxacin in broiler chickens
DE VITO, VIRGINIA;GIORGI, MARIO
2016-01-01
Abstract
Title: Pharmacokinetic and pharmacodynamic evaluations of levofloxacin in broiler chickens Objective: To evaluate the PK/PD and residues of levofloxacin (L) after IV and oral administrations in broiler chickens. Materials & Methods: 65 healthy broiler chickens were randomly divided into 4 groups (A n=20, B n=20, C n=20 and D n=5). Groups A, B and C received 5 mg/kg of L (A and B oral, C IV) while D was the control group. Blood samples were withdrawn at different scheduled times for the group A and C, while animals in group B were sub-divided in to 5 sub-groups (n=4) and euthanized for organ (liver, kidney, muscle, lung) collections at different times (1, 6, 10, 24, 48 h). L concentrations in blood and tissues were quantified by validated HPLC-FL method. PK data of L was fitted using a non-compartment model. As PD studies, two field E. coli isolates were collected from cloacal swabs. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against E.coli (isolated in clinical broilers) were determined in broth and in serum obtained from the healthy animals using the microdilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. In vitro and ex vivo anti-bacterial effects of L were determined using time killing curve. Solutions of L in serum (0.0, 0.03, 0.06, 0.125, 0.25, 0.5 and 1 μg/ml) and serum samples (10, 30 min, 1, 4, 6, 10, 24 and 48 h) were used for the determination of in vitro and ex vivo antibacterial effects against E. coli. In vivo Cmax/MIC and AUC24h/MIC, were calculated by linking PK data with PD index (MIC) for serum after oral administration of L in clinically isolated E. coli. Ex vivo AUC24h/MIC were obtained after 24h incubation from ex vivo time killing curve and fitted using the sigmoidal inhibitory Emax model. Using PK-PD modelling, the optimal oral dose in broilers were predicted. Results & Conclusion: The pharmacokinetic profiles of L after oral and IV administrations were almost overlapping in the elimination phase. The oral F% was 124±39. All the tested organs contained quantifiable L concentrations up to 48 hours. The liver was the most contaminated organ then in descending order kidney, lung and muscle. The results of ex vivo growth inhibition curves were consistent with the in vitro time-kill study. Plasma concentration above 8xMIC led to eradication of E.coli. The MIC and MBC of L in MHB and serum were 0.03, 0.06 and 0.125 μg/mL, respectively. The pharmacokinetic profiles of levofloxacin were similar with those in previous studies in chickens and calves. Levofloxacin showed plasma concentration dependent antibacterial activities against clinical E.coli. A dose of 5 mg/kg of L appears to be able to kill E.coli. Keywords: broiler chickens, levofloxacin, pharmacokinetics, pharmacodynamics, residues References: 1. Giorgi, M., Rota, S., Giorgi, T., Capasso, M., Briganti, A., 2013. Journal of Exotic Pet Medicine 22, 192-199.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
