Pharmacokinetics of florfenicol in blunt‐snout bream (Megalobrama amblycephala) at two water temperatures with single‐dose oral administration

Abstract

The pharmacokinetics and residue elimination of florfenicol (FFC) and its metabolite florfenicol amine (FFA) were studied in healthy blunt‐snout bream (Megalobrama amblycephala, 50 ± 10 g). The study was conducted with a single‐dose (25 mg/kg) oral administration at a water temperature of 18 or 28°C, while in the residue elimination study, fish were administered at 25 mg/kg daily for three consecutive days by oral gavage to determine the withdrawal period (WDT) at 28°C. The FFC and FFA levels in plasma and tissues (liver, kidneys and muscle) were analysed using high‐performance liquid chromatography (HPLC). A no‐compartment model was used to analyse the concentration versus time data of M. amblycephala. In the two groups at 18 and 28°C, the maximum plasma concentration (Cmax) of FFC was 5.89 and 6.21 μg/ml, while the time to reach Cmax (Tmax) was 5.97 and 2.84 hr, respectively. These suggested that higher temperature absorbed more drug and more quickly at M. amblycephala. And the elimination half‐life (T1/2kβ) of FFC was calculated as 26.75 and 16.14 hr, while the total body clearance (CL) was 0.09 and 0.15 L kg−1 hr−1, and the areas under the concentration–time curves (AUCs) were 265.87 and 163.31 μg hr/ml, respectively. The difference demonstrated that the elimination rate of FFC in M. amblycephala at 28°C was more quickly than that at 18°C. The results of FFA showed the same trend in tissues of M. amblycephala. After multiple oral doses (25 mg/kg daily for 3 days), the k (eliminate rate constant) of FFA in M. amblycephala muscle was 0.017, the C0 (initial concentration) was 3.07 mg/kg, and the WDT was 10 days (water temperature 28°C).

Combined Effects of Temperature and Salinity on the Pharmacokinetics of Florfenicol in Nile Tilapia (Oreochromis niloticus) Reared in Brackish Water

“…Other than the possible effect of salinity difference, batch-to-batch variation of Nile tilapia strains between the two experiments may be another possible explanation since different tilapia strains could have different growth performance and adaptability in saline water (46)(47)(48). It is worth mentioning that the directions of change for the AUC, t 1/2β , T max , and MRT (which decrease at a higher temperature) and CL/F (which increase at a higher temperature) of FF were almost consistently observed across various fish species and experimental conditions (20)(21)(22)(23)(24)(25)(26). In contrast, the effects of water temperature on C max and Vd/F were more elusive.…”

“…Despite the fact that many PK data of FF in fish species are available in the literature, most of these studies investigated the PK behavior at only one temperature and one salinity level. Nevertheless, the effect of water temperature on the PK of FF has been assessed in some fish species including Nile tilapia ( 20 ), common carp ( Cyprinus carpio ) ( 21 ), channel catfish ( Ictalurus punctatus ) ( 22 ), Japanese eel ( Anguilla japonica ) ( 23 ), crucian carp ( Carassius auratus ) ( 24 ), Wuchang bream ( Megalobrama amblycephala ) ( 25 ), and spotted halibut ( Verasper variegates ) ( 26 ), whereas the influence of salinity has been studied only in Nile tilapia ( 27 ). Unfortunately, to the best of the author's knowledge, the combined effect of temperature and salinity on the PK of FF has yet to be revealed in any fish species.…”

Evaluation of absorption and depletion of florfenicol in European seabass Dicentrarchus labrax

“…Apparently, as with most pharmacokinetic parameters, maximum plasma concentration values are strongly interspecific as well as experimentally and environmentally dependent (Chang et al., 2019; Feng et al., 2008; Huang et al., 2019; Rairat et al., 2019, 2020) and therefore, should be seriously considered when direct comparisons are attempted among different studies. Water temperature (Chang et al., 2019; Huang et al., 2019; Rairat et al., 2019) and salinity (Feng et al., 2008; Rairat et al., 2020) in particular have been specifically demonstrated as substantial factors affecting the kinetic profile of FLO in farmed fish. In fact, increasing water temperature would cause an increase in blood flow and in drug metabolic rate, leading to enhanced clearance of the drug (Rairat et al., 2019).…”

“…The maximum plasma concentration value of FLO in European seabass was found 1.6 μg/ml which is admittedly lower compared to those calculated after dietary delivery in other farmed fish species (1.8–55 μg/ml) held however in different environmental conditions (Table 4). Apparently, as with most pharmacokinetic parameters, maximum plasma concentration values are strongly interspecific as well as experimentally and environmentally dependent (Chang et al., 2019; Feng et al., 2008; Huang et al., 2019; Rairat et al., 2019, 2020) and therefore, should be seriously considered when direct comparisons are attempted among different studies. Water temperature (Chang et al., 2019; Huang et al., 2019; Rairat et al., 2019) and salinity (Feng et al., 2008; Rairat et al., 2020) in particular have been specifically demonstrated as substantial factors affecting the kinetic profile of FLO in farmed fish.…”

Pharmacokinetics of Free Oxytetracycline and Oxytetracycline Loaded Cockle Shell Calcium Carbonate-Based Nanoparticle in BALB/c Mice

“…The pharmacokinetics of OTC in this study was performed using a non-compartmental model (25,26). Its simplicity, objectivity, and practicability favor its use for description of the time course of drug concentrations in the body (17,27).…”