Pharmacokinetics of Danofloxacin in Gushi Chickens after Single Oral and Intravenous Administration

Abstract

This study aimed to determine the pharmacokinetics of danofloxacin in Gushi chickens after a single oral (PO) and intravenous (IV) dose at 5 mg/kg body weight (BW). Thirty-two Gushi chickens, aged 20 weeks, were selected and divided into two groups at random, with each group consisting of 16 chickens, evenly distributed between males and females. Following danofloxacin administration, blood samples were taken at predetermined time intervals and the plasma was separated. The concentrations of danofloxacin in plasma were quantified by HPLC with a fluorescence detector. Then the concentrations versus time data were subjected to non-compartmental analysis (NCA) using Phoenix software (version: 8.1.0). After administering danofloxacin orally at a dose of 5 mg/kg BW to Gushi chickens, our results demonstrated that the peak concentration reached 0.53 μg/mL at 4 h. The half-life of absorption (t1/2ka) was determined to be 2.37 ± 1.60 h, and the bioavailability (F) was calculated as 40.12 ± 15.83%. For both oral and intravenous administration, the area under the concentration–time curve (AUC0-∞) was determined to be 4.72 ± 1.86 and 11.76 ± 3.25 h·µg/mL, respectively. The corresponding elimination half-life (t1/2λz) was measured as 11.24 ± 3.90 and 10.17 ± 3.72 h. Moreover, the mean residence time (MRT) was calculated as 10.20 ± 2.47 and 7.05 ± 1.97 h for these respective routes. Based on the calculated AUC/MIC ratio values, it can be inferred that the 5 mg/kg BW dosage of danofloxacin, whether administered orally or intravenously, is expected to effectively treat Escherichia coli and Pasteurella multocida infections in Gushi chickens.

In vitro antibacterial activity of danofloxacin against Escherichia coli in Gushi chickens and its residue depletion following multiple oral administration

“…The MIC values for danofloxacin were determined against 42 E. coli isolates, with the MIC 50 established at 0.5 μg/mL ( Figure 1 ). Although this result is higher than previously reported values ranging from 0.015 to 0.25 μg/mL ( Ozawa et al, 2010 ; Rusch et al, 2015 ; Wang et al, 2022 ), the findings suggest that the concentration of danofloxacin in the intestine is adequate for effective eradication of E. coli ( Chen et al, 2023 ). However, it is undeniable that E. coli has developed increased resistance to danofloxacin.…”

“…After multiple administration of danofloxacin at 5 mg/kg BW for 3 d, the C max in plasma was only 0.17 ± 0.119 μg/mL. This result starkly contrasts with a single administration of the same dose in Gushi chickens (0.53 ± 0.19 μg/mL), where the time to peak was 4 h ( Chen et al, 2023 ). The difference in C max values between multiple and single administration may be attributed to the current sampling design.…”

“…It possesses exceptional qualities such as remarkable resistance to coarse feeding, robust disease resistance, and the delectable quality of its meat ( Zhang et al, 2023 ). In contrast to commercially farmed chickens confined in cages, Gushi chickens are bred under a free-range model that makes them highly vulnerable to widespread infections, such as Mycoplasma and Escherichia coli infections ( Chen et al, 2023 ). Consequently, farmers commonly employ antibiotics to address infections in Gushi chickens.…”

“…Notably, danofloxacin not only achieves high concentrations in tissues but also can modify bacterial growth rates and morphology even below its inhibitory concentration ( Lynch et al, 1994 ). This unique capability has led to its approval in numerous countries for treating diseases such as E. coli infections, Mycoplasma infections, and pneumonia in poultry ( Chen et al, 2023 ). Recognized for its efficacy, particularly in addressing respiratory diseases and bacterial infections in poultry, danofloxacin stands as an ideal drug for these applications ( Zhang et al, 2020 ).…”