Pharmacokinetic-Pharmacodynamic Modelling of Danofloxacin in Turkeys |
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| Authors: | A M Haritova N V Rusenova P R Parvanov L D Lashev J Fink-Gremmels |
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| Institution: | (1) Department of Pharmacology, Physiology and Chemistry, Bulgaria;(2) Department of Microbiology, Infectious and Parasitic Diseases, Section of Microbiology, Faculty of Veterinary Medicine, Trakia University, Bulgaria;(3) Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands |
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| Abstract: | Colibacillosis is a systemic disease responsible for important economic losses in poultry breeding; fluoroquinolones, including
danofloxacin, are used to treat diseased animals. The purpose of the present study was to estimate pharmacokinetic–pharmacodynamic
(PK-PD) surrogates for bacteriostasis, bactericidal activity and bacterial elimination against Escherichia coli O78/K80, using a PK-PD approach, for danofloxacin in turkeys after oral administration. Eight healthy turkeys, breed BUT
9, were included in a two-way crossover study. The drug was administered intravenously (i.v.) and orally at a dose rate of
6 mg/kg bw. The values of the elimination half-life and the total body clearance after i.v. administration were 8.64 ± 2.35
h and 586.76 ± 136.67 ml kg-1h-1, respectively. After oral administration, the values of the absolute bioavailability and the elimination half-life were 78.37±
17.35% and 9.74± 2.93 h, respectively. The minimum inhibitory concentration against the investigated strain in turkey serum
was 0.25 μg/ml, four times higher than in broth. The lowest effective ex vivo AUC24/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coliO78/K80 were 0.416 h, 1.9 h and 6.73 h, respectively. The oral dose of 6 mg/kg used in the present study could be interpreted
as being sufficient to eliminate E. coli with an MIC 0.25 μ g/ml. However, considering the demand that antimicrobial resistance should be avoided by complete bacterial
elimination, PK-PD considerations suggest that an even higher dose of 32 mg/kg per day or 0.7 mg/kcal per day should be evaluated
in clinical trials. |
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| Keywords: | pharmacokinetic– pharmacodynamic modelling danofloxacin turkeys |
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