Population pharmacokinetics for danofloxacin in the intestinal contents of healthy and infected chickens

Abstract

Avian pathogenic Escherichia coli could cause localized and systemic infection in the poultry, and danofloxacin is usually used to treat avian colibacillosis through oral administration. To promote prudent use of danofloxacin and reduce the emergence of drug‐resistant E. coli strains, it is necessary to understand the population pharmacokinetics (PopPK) of danofloxacin in chicken intestines. In this study, reversed‐phase high performance liquid chromatography (HPLC) with fluorescence detection was used to detect the concentrations of danofloxacin in the contents of duodenum, jejunum, and ileum of the healthy and infected chickens after single oral administration (5 mg/kg body weight). Then, the PopPK of danofloxacin in intestines were analyzed using NONMEM software. As a result, a two‐compartment PK model best described the time‐concentration profile of duodenal, jejunal, and ileal contents. Interestingly, absorption rate (Ka), distribution volume (V), and clearance (CL) for danofloxacin from duodenal, jejunal to ileal contents were sequentially decreased in the healthy chickens. However, the trend of Ka, V, and CL of danofloxacin was changed dramatically in the intestine of infected chickens. Ka and V of danofloxacin in the jejunum were higher than in the ileum and duodenum. Compared with healthy chickens, Ka and V of danofloxacin in the duodenum decreased significantly, while increased in jejunum, respectively. It has been noted that Ka decreased and V increased in the ileum of infected chickens. Besides, CL in the duodenum, jejunum, and ileum of infected chickens was, respectively, lower than those of healthy chickens. Interestingly, the relative bioavailability (F) of danofloxacin in the ileum was relatively higher in both healthy and infected chickens. In addition, F in the duodenal, jejunal, and ileal contents of infected chickens was respectively higher than healthy chickens. In summary, the PopPK for danofloxacin in infected chicken intestines was quite different from healthy chickens. The absorption, distribution, and clearance of danofloxacin in healthy chickens decreased from duodenum to jejunum and to ileum. Moreover, the pharmacokinetic characteristics in the intestine of infected chickens changed significantly, and the pharmacokinetic characteristics in the ileum can be used as a representative of all intestinal segments.

The influence of immune stress induced by Escherichia coli lipopolysaccharide on the pharmacokinetics of danofloxacin in broilers

“…The detection method referred to Tian ( Tian et al, 2019 ) with some adjustments. Waters 2695 high-performance liquid chromatography ( HPLC ) system (Waters) was used in this study, and the separation was accomplished on a reversed-phase chromatographic column (Hypersil BDS C18; 4.6 mm × 250 mm, 5 µm; Dalian Elite Analytical Instruments Co., Ltd.) at 30°C.…”

Influence of Escherichia coli endotoxemia on danofloxacin pharmacokinetics in broilers following single oral administration

“…The detection method referred to Tian et al (2019) with some adjustments. Briefly, 200 μl of plasma samples were treated with two volumes of acetonitrile, vortex mixed for 30 s, and centrifuged at 15,000 g for 10 min at 4°C.…”

“…The recommended dosage of danofloxacin in broilers by the Chinese national veterinary drug database is 2.5–5 mg/kg BW (calculated as danofloxacin), once a day for 3 days. In other studies conducted in broilers, the oral dose was also 5 mg/kg BW (Knoll et al, 1999; Tian et al, 2019; Zeng et al, 2011). Therefore, this study aimed to determine the potential impact of E .…”

“…The recommended dosage of danofloxacin in broilers by the Chinese national veterinary drug database is 2.5-5 mg/kg BW (calculated as danofloxacin), once a day for 3 days. In other studies conducted in broilers, the oral dose was also 5 mg/kg BW (Knoll et al, 1999;Tian et al, 2019;Zeng et al, 2011). Therefore, this study aimed to determine the potential impact of E. coli endotoxemia on the pharmacokinetics of danofloxacin in broilers by administering a single oral dose of 5 mg/kg BW 1 h after intravenous injection of LPS at a dose of 2.5 mg/kg BW to broilers.…”

Dual-mode immunoassay system based on glucose oxidase-triggered Fenton reaction for qualitative and quantitative detection of danofloxacin in milk

“…Danofloxacin (DAN) is a third-generation animalspecific fluoroquinolone with wide antibacterial spectrum and strong bactericidal activity (Aliabadi and Lees, 2003). It has high concentration in animal lung tissue and good antibacterial effect on respiratory pathogens (Tian et al, 2019). According to Announcement No.…”