Pharmacokinetic-pharmacodynamic modelling of danofloxacin in turkeys.
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(-1)h(-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 microg/ml, four times higher than in broth. The lowest effective ex vivo AUC(24)/MIC ratios required for bacteriostasis, bactericidal activity, and total killing of E. coli O78/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 microg/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.
Haritova
A M
AM
Department of Pharmacology, Physiology and Chemistry, Trakia University, Bulgaria.
Rusenova
N V
NV
Parvanov
P R
PR
Lashev
L D
LD
Fink-Gremmels
J
J
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000662:veterinary*; D005260:Female; D024841:Fluoroquinolones / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D011201:Poultry Diseases / Q000188:drug therapy*; D014422:Turkeys / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C068581:danofloxacin