Population Pharmacokinetics of Danofloxacin in Yellow River Carp (Cyprinus carpio haematopterus) After One Single Oral Dose

Abstract

This study aimed to determine the population pharmacokinetics of danofloxacin in healthy Yellow River carp (Cyprinus carpio Haematopterus) after single oral administration at 10 mg/kg body weight (BW). A sparse sampling was applied in this study and plasma samples were randomly collected from the tail veins of six carp at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 and 144 h after administration. A maximum of four plasma samples was collected from each carp. Then the concentrations of danofloxacin in plasma samples were determined through an HPLC method. Danofloxacin could be quantified in plasma up to 144 h after administration. The corresponding population pharmacokinetic modeling was developed according to the non-linear mixed effect method, including covariate and covariance models to explain some variations from unknown sources and improve the prediction ability. On the premise of sparse sampling, the typical values of the population (fixed effect) and inter-individual variation (random effect) were described by the current population pharmacokinetic model. The estimated typical values and coefficient of variation between individuals (CV%) of absorption rate constant (tvKa), apparent distribution volume (tvV) and clearance (tvCL) were 2.48 h−1 and 0.203%, 47.8 L/kg and 8.40%, 0.694 L/h/kg and 4.35%, respectively. The current danofloxacin oral dosing (10 mg/kg BW) can provide suitable plasma concentrations to inhibit those pathogens with MIC values below 0.016 μg/ml based on the calculated PK/PD indices of AUC/MIC or Cmax/MIC. Further studies are still needed to determine the in vitro and in vivo antibacterial efficacy of danofloxacin against pathogens isolated from Yellow River carp and finally draw a reasonable dosing regimen.

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

“…Adjusting the sampling schedule to capture earlier time points could provide a more comprehensive understanding of the peak concentration dynamics after repeated administration. Similar trends were observed in other studies, such as the research on Yellow River carp ( Song et al, 2022 ; Song et al, 2023 ), where the C max after a single dose (0.166 ± 0.321 μg/mL) exceeded that after 5 consecutive days of oral administration (0.121 ± 0.066 μg/mL). In broilers, the C max after a single dose (0.73 μg/mL) was higher than that after 5 consecutive days of drinking water administration (0.044 μg/mL) ( Lynch et al, 1994 ), suggesting a potential establishment of a stable state for danofloxacin in the body.…”

Pharmacokinetics of danofloxacin after single oral and intravenous administration in non‐laying hens

“…This is the first pharmacokinetic study of danofloxacin in non-laying hens. Danofloxacin was orally and intravenously given to hens at 5 mg/kgbodyweight(BW).Differentdoseshavebeenusedinother species, such as 1.25 mg/kg BW in cattle and sheep (Karademir et al, 2015;Kum et al, 2009;Sappal et al, 2009)or10 mg/kgBW in fish species (Parker-Graham et al, 2020;Song et al, 2022). In China, danofloxacin has been approved for oral administration to chickensviamedicatedfeedatlabeleddosesof2.5-5 mg/kgBWfor 3 consecutive days.…”

Population Pharmacokinetics of Difloxacin in Crucian Carp (Carassius auratus) after a Single Oral Administration

“…To achieve precise dosing in each fish, difloxacin was administered via gavage at a rate of 20 mg/kg body weight. As described previously [ 18 ], a 1-mL syringe was used to accurately aspirate the drug solution and slowly push the difloxacin solution through a plastic hose from the mouth of the fish into the belly. To prevent possible reflux, each fish was restrained for about 20 s after administration.…”

“…The collected blood was then immediately placed in test tubes containing heparin. Table 1 shows the schedule of blood collection [ 18 ]. Each fish was sparsely sampled three times ( Table 1 ).…”

“…Population pharmacokinetics is an effective means of expalining the random effects of drugs on subjects [ 16 , 17 ]. It encompasses inter-individual and intra-individual/inter-experiment random variations, which can solve the problem that small animal such as fish cannot be continuously sampled [ 18 ]. Within the field of aquaculture medicine, population pharmacokinetics has gained popularity, and extensive research has been conducted on aquaculture animals, including rainbow trout [ 19 ], Yellow River carp [ 18 ], tilapia [ 20 ], giant freshwater prawns [ 21 ], and turtles [ 22 ].…”