Study Highlights Need to Revise Flumequin Dose Levels16 December 2013
ITALY - Researchers investigating the pharmacokinetic and pharmacodynamic characteristics of the antibiotic, flumequine, in the treatment of colibacillosis in turkeys suggest that the dosage scheme should be reviewed.
Based on these results, flumequine (FLU) administration should be adopted when specific diagnostic findings indicate its efficacy, according to a group of researchers from across Italy. In a paper published in Poultry Science, they added that revising the dosage scheme to comply with the prudent and responsible use of antimicrobials in veterinary medicine is advisable.
FLU is used in the treatment of systemic bacterial infections in poultry, including colibacillosis, which is a common disease in turkeys, report first-named author, C. Ferraresi from the University of Milan and co-authors there and in Padua and Pisa.
The pharmacokinetic (PK) behaviour of FLU administered to 32 healthy turkeys as an oral bolus via gavage or as 10-hour pulsed administration in drinking water were compared, using the authorised dose of 15mg per kg and the double dose of 30mg per kg.
The minimum inhibitory concentrations (MIC) of 235 Escherichia coli field strains isolated from poultry were determined for pharmacodynamics (PD) to develop a PK/PD model. Blood samples were collected at established times over 24 hours, and the obtained plasma was analysed using a liquid chromatography tandem mass spectrometry method that was validated in-house.
A mono-compartmental model and a non-compartmental model were applied to the data to obtain the PK results.
For both types of administration and both dosages, the ratios of the maximum concentration (Cmax)/MIC50 and the area under the plasma concentration-time curve (AUC)/MIC50 achieved were considerably lower than the fluoroquinolone break-points usually adopted for efficacy.
The Cmax/MIC50 and AUC0–24/MIC50 ratios were, respectively, 0.67 ± 0.09 and 4.76 ± 0.48 and 1.18 ± 0.35 and 7.05 ± 2.40 for the 15 and 30mg per kg bolus doses, respectively.
After 10-hour pulsed administration of 15mg per kg, values of Cmax/MIC50, 0.19 ± 0.02 on day 1 and 0.30 ± 0.08 on day5 of therapy were obtained, the AUC/MIC50 ratios were 2.09 ± 0.29 and 3.22 ± 0.93 on days 1 and 5, respectively.
Higher values were obtained with the doubled dose of 30mg per kg: the Cmax/MIC50 ratios were 0.49 ± 0.11 on day 1 and 0.69 ± 0.18 on day 5; the AUC/MIC50 ratios were 5.15 ± 1.15 and 6.57 ± 1.92 on days 1 and 5, respectively.
Ferraresi C., L. Lucatello, V. Meucci, L. Intorre, G. Grilli, A. Piccirillo, E. Russo, R. Villa, C. Montesissa and P. Cagnardi. 2013, Pharmacokinetic/pharmacodynamic evaluation of the efficacy of flumequine in treating colibacillosis in turkeys. Poult. Sci. 92(12):3158-3165. doi: 10.3382/ps.2013-03460
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