Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida‐infected Gaoyou ducks

Abstract

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (Cmax) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The Cmax and AUC0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.

Pharmacokinetics of thiamphenicol in Japanese quails (Coturnix japonica) after single intravenous and oral administrations

“…The peak plasma concentrations (C max ) following PO administration of TP in quails were 19.81 μg/ml, being reasonably similar to that reported for TP in ducks 20.27 μg/ml (Tikhomirov et al, 2019) and higher than TP (8.99 μg/ml) in turkeys (Switała et al, 2007) and FF (17.86 μg/ml) observed in ducks (Lan et al, 2019). The absorption process was rapid with time to reach maximum concentration (t max ) of 2.00 hr, which was similar to FF (2.00 hr) in turkeys (Switała et al, 2007) and longer than TP (1.42 hr) in turkeys (Kowalski, 2007), FF (0.50 hr) in ducks (Lan et al, 2019), and shorter than TP (4.57 hr) in turkeys (Switała et al, 2007).…”

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“…A model of P. multocida infection was established according to our previous study with three isolates of different susceptibility (Lan et al, 2019). Briefly, strains 0825Y 1 (sensitive to all five antimicrobial agents), 0901J 1 (sensitive to florfenicol, but resistant to gentamicin and enrofloxacin), and JY160110 (resistant to all antimicrobial agents except gentamicin) were grown in broth overnight.…”

“…The florfenicol concentration in serum was determined using high-performance liquid chromatography (HPLC) as we reported previously (Lan et al, 2019). Briefly, florfenicol was extracted with 2 ml of ethyl acetate, dried in a nitrogen stream, and dissolved in 0.2 ml of mobile phase [water and acetonitrile at 75:25 (vol:vol)].…”

“…Florfenicol is a phenicol and has been approved to prevent and treat infectious diseases in animals (Pilehvar et al, 2016;Lan et al, 2019). Because of its strong antibacterial effect against Grampositive and Gram-negative bacteria as well as bacteria resistant to thiamphenicol, florfenicol has an important role in the poultry industry.…”

“…Sidhu and colleagues found that florfenicol showed a bactericidal effect in serum, transudates and exudates with an AUC 0−24 h /MIC of 18.06, 17.34, and 17.86, respectively, using ex vivo PK/PD modeling in calves (Sidhu et al, 2014). PK/PD studies of florfenicol have also been undertaken in aquatic livestock (Bourely et al, 2019;Lan et al, 2019). From those studies, we can conclude that florfenicol shows good antibacterial activity against respiratory pathogens and that the best PK/PD parameter is AUC 0−24 h /MIC.…”