Integration of Pharmacokinetic and Pharmacodynamic Indices of Marbofloxacin in Turkeys

Abstract

Fluoroquinolones are extensively used in the treatment of systemic bacterial infections in poultry, including systemic Escherichia coli bacillosis, which is a common disease in turkey flocks. Marbofloxacin has been licensed for use in various mammalian species, but not as yet for turkeys, although its kinetic properties distinguish it from other fluoroquinolones. For example, the longer half-life of marbofloxacin in many animal species has been appreciated in veterinary practice. It is generally accepted that, for fluoroquinolones, the optimal dose should be estimated on the basis of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the drug under consideration. Knowledge of these specific data for the target animal species allows the establishment of an integrated PK-PD model that is of high predictive value. In the present study, the antibacterial efficacy (PD indices) against a field isolate of Escherichia coli O78/K80 was investigated ex vivo following oral and intravenous administration of marbofloxacin to turkeys (breed BUT 9; six animals per group) at a dose of 2 mg/kg of body weight (BW). At the same time, the serum concentrations of marbofloxacin were measured at different time intervals by a standardized high-performance liquid chromatography method, allowing the calculation of the most relevant kinetic parameters (PK parameters). The in vitro serum inhibitory activity of marbofloxacin against the selected E. coli strain, O78/K80, was 0.5 g/ml in the blood serum of turkeys, and the ratio of the maximum concentration of the drug in serum to the serum inhibitory activity was 1.34. The lowest ratio of the measured serum concentration multiplied by the incubation period of 24 h to the serum inhibitory activity required for bacterial elimination was lower than the ratio of the area under the serum concentration-time curve (AUC) to the serum inhibitory activity. These first results suggested that the recommended dose of 2 mg/kg BW of marbofloxacin is sufficient to achieve a therapeutic effect in diseased animals. However, considering the risk of resistance induction, the applied dose should be equal to an AUC/MIC of >125, the generally recommended dose for all fluoroquinolones. According to the PK-PD results presented here, a dose of 3.0 to 12.0 mg/kg BW per day would be needed to meet this criterion. In conclusion, the results of the present study provide the rationale for an optimal dose regimen for marbofloxacin in turkeys and hence should form the basis for dose selection in forthcoming clinical trials.Marbofloxacin is a synthetic fluoroquinolone, developed for veterinary use only (47). It has a broad spectrum of activity (58), and bactericidal concentration-dependent killing is observed against many gram-negative bacteria (12, 49, 51, 52). The pharmacokinetic (PK) properties of marbofloxacin have been studied in several mammalian species, and some advantages over other fluoroquinolones, such as a longer elimination half-life, have been described (2,43,47,48). In practice, this would e...

Plasma and Tissue Disposition of Moxifloxacin in Japanese Quail (Coturnix japonica)

“…This finding was previously reported for moxifloxacin in rabbits, 8 broiler chickens, 10 and ducks 11 and is in agreement with results of other studies of fluoroquinolones in broiler chickens, 17 turkeys, 24 and rabbits. 25 After intravenous administration, moxifloxacin in quail was rapidly distributed with half-lives of distribution of 0.3 hours, similar to results of moxifloxacin in broiler chicks at 0.26 hours 10 and 11 Moxifloxacin is slowly eliminated with an elimination half life of 2.18 hours, which is lower than that reported for danofloxacin in broiler chickens, turkeys, rabbits, and quail of 6.73, 8.64, 4.88, and 2.52 hours, respectively.…”

“…The absorption process was rapid with T max ¼ 1.40 hours for intramuscular and T max ¼ 1.87 hours for oral administration, with k ab ¼ 1.12 and 0.76 h À1 and absorption half-life of 0.62 and 0.91 hours, for intramuscular and oral administration, respectively. These values of bioavailability are consistent with those reported for moxifloxacin in rabbits, broilers, and ducks 8,10,11 ; are in agreement with those reported for danofloxacin in broilers 17 and marbofloxacin in turkeys 24 ; and are higher than that reported for pefloxacin in ducks. 29 Effective use of concentration-dependent fluoroquinolones such as moxifloxacin while preventing selection for resistance has been associated with reaching C max 8-10 times the MIC for the pathogenic organism, rather than maintaining a concentration above MIC (time .…”

Bioavailability pharmacokinetics and residues of marbofloxacin in normal and E.coli infected broiler chicken

“…These values were similar to marbofloxacin (1.05±0.15 μg/ml) in broiler chickens (Anadon et al, 2002). Conversely, the reported maximum serum concentration in present study was lower than those recorded in quails 3.59±0.24 µg/ml (Aboubakr and Abdelazem, 2015) On the other hand, the acquired result of maximum serum concentration was higher than in turkey 0.80±0.32 µg/ml (Haritova et al, 2006 Goudah and Hasabelnaby, (2010). These distinctions are moderately basic and are as often as possible identified with between species variety, test techniques utilized, measure of time between blood inspecting and/or the wellbeing status and age of the creature (Haddad et al, 1985).…”

Pharmacokinetics of Marbofloxacin Following Single and Repeated Dose Intravenous Administration in Broiler Chickens

“…This covers MIC 90 value of 0.125-0.20 g/mL against most common E. coli and other gram-negative bacterial infections except P. aeurgenosa in chickens and other birds (Spreng et al, 1995;Haritova et al, 2006 (Anadon et al, 2002). Findings of present study, indicated that the drug was rapidly distributed in the body fluids and then relatively slowly eliminated from the body in broiler chickens after single and repeated i.v.…”