Pharmacokinetic-Pharmacodynamic Modelling of Danofloxacin in Turkeys

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(-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.

Integration of Pharmacokinetic and Pharmacodynamic Indices of Marbofloxacin in Turkeys

“…In chickens, marbofloxacin was absorbed to a lesser extent (F ϭ 56.8%), but the C max was achieved earlier (6). In comparison to danofloxacin (F ϭ 78.4%) and enrofloxacin (F ϭ 69.85%), marbofloxacin has a higher oral bioavailability (25,26). The oxadiazine cycle in the marbofloxacin molecule, which makes it different from other fluoroquinolones, seems to determine the higher oral bioavailability and the increased elimination halflife.…”

Disposición de danofloxacina en plasma y en tejidos comestibles de pollos parrilleros

“…El t½β obtenido de 7,6 h es similar al hallado en pollos de 7,31 h (16) e inferior a las 13,05 ± 1,68 h en pollos (19) y 9,74 ± 2,93 h en pavos (20). El TMR encontrado en esta experiencia de 9,6 h, respecto a experiencias realizadas en pollos, es inferior al obtenido con danofloxacina en pollos de 8,69 h (15) y 15,17± 4,37 h en pavos (20).…”

“…El TMR encontrado en esta experiencia de 9,6 h, respecto a experiencias realizadas en pollos, es inferior al obtenido con danofloxacina en pollos de 8,69 h (15) y 15,17± 4,37 h en pavos (20). Estos valores concuerdan con los antecedentes de moderada permanencia plasmática de fluoroquinolonas en pollos (29), similar a lo que sucede con danofloxacina en mamíferos domésticos (30,31).…”

“…La curva de disposición plasmática generó un ABC de 10 µg-h/ml, mayores a los valores registrados en esta especie utilizando idéntica dosis de danof loxacina (15)(16)(17)19) y en pavos, tras la aplicación de 6 mg/kg (20). La rápida declinación plasmática verificada desde las 12 h no resulta solo de los procesos de eliminación, sino también de la distribución a los tejidos, lo cual es similar a lo observado en experiencias realizadas en pollos (15).…”

“…En esta especie demostró moderada permanencia en el organismo, según reflejan el t½β y el TMR de 9,7 ± 2,9 y 15,1 ± 4,3 h, respectivamente (20).…”