Pharmacokinetic characteristics of florfenicol in green sea turtles (Chelonia mydas) and hawksbill sea turtles (Eretmochelys imbricata) after intramuscular administration.

The pharmacokinetics of florfenicol (FFC) in green sea and hawksbill sea turtles were evaluated following intramuscular (i.m.) administration at two different dosages of 20 or 30 mg/kg body weight (b.w.). This study (longitudinal design) used 5 green sea and 5 hawksbill sea turtles for the two dosages. Blood samples were collected at assigned times up to 168 h. FFC plasma samples were analyzed using validated high-performance liquid chromatography equipped with diode array detection. The pharmacokinetic analysis was performed using a non-compartment approach. The FFC plasma concentrations increased with the dosage. The elimination half-life was similar between the treatment groups (range 19-25 h), as well as the plasma protein binding (range 18.59%-20.65%). According to the surrogate PK/PD parameter (T > MIC, 2 µg/mL), the 20 and 30 mg/kg dosing rates should be effective doses for susceptible bacterial infections in green sea and hawksbill sea turtles.

Bath immersion pharmacokinetics of florfenicol in Nile tilapia (Oreochromis niloticus).

Drug administration by immersion can be a preferable method in certain conditions especially for treating small-sized, anorexic, or valuable fish. Pharmacokinetic information regarding bath treatment is considerably lacking in comparison to other common administration routes. The current study aimed to investigate if immersion can be an effective route to administer florfenicol (FF) for treatment in Nile tilapia. Nile tilapia reared at 28°C were immersed with FF solution at concentrations of 50, 100, 200, 500, and 500/200 (3 hr/117 hr) ppm for 120 hr and moved to drug-free freshwater for another 24 hr. The serum FF concentration in 100, 200, and 500/200 ppm groups reached steady-state at 12 hr with concentrations of 2.44, 3.04, and 5.26 µg/ml, respectively, which were about 2% of the bathing concentrations. The target therapeutic levels of 1-4 µg/ml were attained and maintained within 1-12 hr, depending on the immersion concentration and the target MIC. Serum FF reached the target with shorter time at higher bathing concentration. Following the 120-hr bath, the serum FF declined with the first-order half-life of approximately 10 hr. A minimum of 100 ppm FF is required for treatment purpose, and an initial high loading concentration followed by maintenance concentration is a plausible way to reach in vivo therapeutic level in short time. Greater than 99% of the residual FF in the bathing water could be removed within 15 min by 0.05% NaOCl. Our results indicated that bath immersion is a promising potential route for FF administration in Nile tilapia.

Comparison of florfenicol pharmacokinetics in Exopalaemon carinicauda at different temperatures and administration routes.

Florfenicol is a broad-spectrum antibacterial drug. Exopalaemon carinicauda is important in the prawn aquaculture industry in China. Florfenicol pharmacokinetics in E. carinicauda were studied at different temperatures and via different routes of administration to provide a scientific basis for the rational use of drugs for E. carinicauda production. At water temperatures of 22 ± 0.4°C and 28 ± 0.3°C, after intramuscular (IM) injection and oral (per ora (PO)) administration of florfenicol at 10 mg/kg body weight (BW) and 30 mg/kg BW, respectively, the florfenicol concentration in the plasma, hepatopancreas, gills, muscles, and carapace of E. carinicauda was determined by high-performance liquid chromatography. After IM injection at different temperatures, the metabolism of florfenicol in E. carinicauda conformed to a two-compartment open model with zero-order absorption. After PO administration, the metabolism of florfenicol in E. carinicauda was consistent with a two-compartment open model with first-order absorption. Using an identical administration route but different water temperatures, the metabolism of florfenicol in E. carinicauda was quite different. Overall, florfenicol was absorbed rapidly and distributed widely in E. carinicauda, but elimination was slow and the bioavailability was not high. A low temperature and PO administration resulted in a low elimination rate.

Pharmacokinetic profiles of florfenicol in spotted halibut, Verasper variegatus, at two water temperatures.

The pharmacokinetic profiles of florfenicol in the spotted halibut (Verasper variegatus) were investigated at 15 and 20°C water temperatures, respectively. Florfenicol content in plasma samples was analyzed using an HPLC method. Drug concentration versus time data were best fitted to a three-compartment model after a single intravenous administration (15 mg/kg BW), and fitted to a two-compartment model after an oral administration (30 mg/kg BW) at 15 and 20°C. The florfenicol concentration in the blood increased slowly during the 12 hr following an oral administration at 15°C, with a peak concentration (Cmax ) of 9.1 mg/L, and then declined gradually. The half-lives of absorption, distribution, and elimination phase were 2.18, 5.66 and 14.25 hr, respectively. The bioavailability (F) was calculated to be 24.14%. After an oral administration at 20°C, shorter half-lives of absorption (1.33 hr), distribution (2.51 hr) and elimination (9.71 hr), a higher Cmax (12.2 mg/L), and a similar F (23.98%) were found. Based on the pharmacokinetics and pharmacodynamics, an oral dose of 30 mg/kg BW was suggested to be efficacious for bacterial disease control in spotted halibut farming.

Pharmacokinetics of florfenicol and thiamphenicol in ducks.

The pharmacokinetics of florfenicol (FF) and thiamphenicol (TP) after single intravenous (IV) and oral (PO) administration was investigated in Mulard ducks. Both antibiotics were administered at a dose of 30 mg/kg body weight, and their concentrations in plasma samples were assayed using high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were calculated using a noncompartmental method. After IV administration, significant differences were found for the mean residence time (2.25 ± 0.21 hr vs. 2.83 ± 0.50 hr for FF and TP, respectively) and the general half-life (1.56 ± 0.15 hr vs. 1.96 ± 0.35 hr for FF and TP, respectively) indicating slightly slower elimination of TP as compared to FF. The clearance, however, was comparable (0.30 ± 0.07 L/hr/kg for FF and 0.26 ± 0.04 L/hr/kg for TP). The mean volume of distribution was below 0.7 L/kg for both drugs. Pharmacokinetics after PO administration was very similar for FF and TP suggesting minor clinical importance of the differences found in the IV study. Both antimicrobials showed rapid absorption and bioavailability of more than 70% indicating that PO route should be an efficient method of FF and TP administration to ducks under field conditions.

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

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 (T½ß : 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.

Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK-PD modeling analysis in pigs.

Florfenicol, a structural analog of thiamphenicol, has broad-spectrum antibacterial activity against gram-negative and gram-positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic-pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK-PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 µg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time-killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr , AUC0-∞ , Tmax , T1/2 , Cmax , CLb, and Ke were 49.83, 52.33 µg*h/ml, 1.32, 10.58 hr, 9.12 µg/ml, 0.50 L/hr*kg, 0.24 hr-1 and 134.45, 138.71 µg*hr/ml, 2.05, 13.01 hr, 16.57 µg/ml, 0.18 L/hr*kg, 0.14 hr-1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 µg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 µg/ml) for clinical use, but these predicted data should be validated in the clinical practice.

Comparative single-dose pharmacokinetics of orally administered florfenicol in rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) at health and experimental infection with Streptococcus iniae or Lactococcus garvieae.

This study evaluates changes in the pharmacokinetic behavior of a single oral dose of florfenicol in rainbow trouts experimentally infected with Lactococcus garvieae or Streptococcus iniae. One hundred and fifty fish were randomly divided into three equal groups: 1-healthy fish, 2-fish inoculated with S. iniae (2.87 × 107 CFU/ml, i.p.), and 3-fish inoculated with L. garvieae (6.8 × 105 CFU/ml, i.p.). Florfenicol was administered to all groups at 15 mg/kg by oral gavage. Blood sampling was performed at 0, 2, 3, 6, 8, 12, 24, 48, 72, and 120 hr after drug administration to each group, and plasma concentration of florfenicol was assayed by HPLC method. The MICs of florfenicol were 1.2 µg/ml and 5 µg/ml against L. garviae and S. iniae, respectively. Healthy fish showed higher values for most of the PK/PD parameters as compared to fish infected with L. garvieae which was reversed in fish infected with S. iniae. Fish infected with L. garvieae showed decreased relative bioavailability accompanied by increased volume of distribution at steady-state (Vdss ) and total body clearance (ClB ). Infection with S. iniae increased the peak concentration of drug after administration (Cmax) and decreased elimination half-life (T1/2 ß ), central compartment volume (Vc ), and Vdss . In conclusion, infection with these bacteria can affect the pharmacokinetic behavior of florfenicol in rainbow trouts as shown by decreased bioavailability and increased total body clearance and volume of distribution in L. garvieae infection and decreased volume of distribution accompanied by increased Cmax in S. iniae-infected fish.

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration.

Bayesian population pharmacokinetic models of florfenicol in healthy pigs were developed based on retrospective data in pigs either via intravenous (i.v.) or intramuscular (i.m.) administration. Following i.v. administration, the disposition of florfenicol was best described by a two-compartment open model with the typical values of half-life at α phase (t1/2α ), half-life at ß phase (t1/2ß ), total body clearance (Cl), and volume of distribution (Vd ) were 0.132 ± 0.0289, 2.78 ± 0.166 hr, 0.215 ± 0.0102, and 0.841 ± 0.0289 L kg-1 , respectively. The disposition of florfenicol after i.m. administration was best described by a one-compartment open model. The typical values of maximum concentration of drug in serum (Cmax ), elimination half-life (t1/2Kel ), Cl, and Volume (V) were 5.52 ± 0.605 µg/ml, 9.96 ± 1.12 hr, 0.228 ± 0.0154 L hr-1  kg-1 , and 3.28 ± 0.402 L/kg, respectively. The between-subject variabilities of all the parameters after i.m. administration were between 25.1%-92.1%. Florfenicol was well absorbed (94.1%) after i.m. administration. According to Monte Carlo simulation, 8.5 and 6 mg/kg were adequate to exert 90% bactericidal effect against Actinobacillus pleuropneumoniae after i.v. and i.m. administration.

Pharmacokinetics of florfenicol and its metabolite florfenicol amine in crucian carp (Carassius auratus) at three temperatures after one single intramuscular injection.

The pharmacokinetic profiles of florfenicol (FF) or florfenicol amine (FFA) in crucian carp were compared at different water temperatures after single intramuscular administration of FF at 10 mg/kg bodyweight. The concentrations of FF and FFA were determined by a high-performance liquid chromatography method, and then, the concentration versus time data were subjected to compartmental analysis using a one-compartment open model. At the water temperatures of 10, 20, and 25°C, the peak concentrations (Cmax s) of FF were 2.28, 2.29, and 2.34 µg/ml, respectively, while those of FFA were 0.42, 0.71, and 0.82 µg/ml, respectively. And the absorption half-life (t1/2ka ) of FF was 0.21, 0.19, and 0.21 hr, while the elimination half-life (t1/2kel ) was 31.66, 24.77, and 21.48 hr, respectively. For FFA, the formation half-life (t1/2kf ) was 3.85, 8.97, and 12.43 hr, while the t1/2kel was 58.34, 30.27, and 21.22 hr, respectively. The results presented here demonstrated that the water temperature had effects on the elimination of both FF and FFA and the formation of FFA. Based on the T > MIC values calculated here, to treat the infections of bacterial with MIC value ≤ 0.5 µg/ml, FF intramuscularly given at 10 mg/kg bodyweight with a 72-hr interval is sufficient at the water temperature of 10°C, while the intervals of 60 and 48 hr were needed at 20 and 25°C, respectively. But to treat bacterial with higher MIC values, more FF or FF at 10 mg/kg BW but with shorter intervals should be intramuscularly given to the infected fish.

Tissue distribution and elimination features of florfenicol in hybrid sturgeon cultured in cool water.

In order to understand pharmacokinetics in vivo and tissue residues of florfenicol in Hybrid sturgeon cultured in cold water, changes in concentration of florfenicol in plasma, muscle, liver and kidney of sturgeon after administration were measured by high performance liquid chromatography mass spectrometry. The results show that after 15.0 mg/kg dose administration, the concentration change in plasma and liver, kidney and muscle of sturgeon are suitable for the one compartment open model. Florfenicol pharmacokinetic parameters in plasma, liver, kidney and sturgeon muscle showed that the peak concentration (Cmax ) were 549.7, 551.8, 958.2 and 405.4 µg/kg, respectively. The peak time (Tmax ) was 17.5, 14.2, 14.0 and 20.8 hr, respectively. The elimination half-life (T1/2 ) was 75.1, 99.8, 68.8 and 75.5 hr, respectively. Area under the curve were 70,048.9, 63,850.6, 109,579.9 and 53,437.3 µg/kg hr, respectively. Mean residence time was 100.6, 96.4, 96.5 and 104.6 hr, respectively. The absorption speed and elimination of florfenicol in cold water cultured sturgeon is slow, and the peak concentration is low, but the florfenicol was widely distributed in the body of sturgeon. The results provide a theoretical basis for formulation of medication and withdrawal period of florfenicol used in sturgeon cultured in cold water.

Preparation, characterization, and pharmacokinetics in swine of a florfenicol enteric formulation prepared using hot-melt extrusion technology.

The objective of this work was to manufacture an enteric formulation of florfenicol (FF) using hot-melt extrusion (HME) technology and to evaluate its in vitro dissolution and in vivo pharmacokinetics. For the HME process, hypromellose acetate succinate LG (HPMCAS-LG) was the enteric polymer mixed with FF, and the two components were extruded with a standard screw configuration at a speed of 50 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FT-IR) were performed to characterize the HME extrudate. The release percentage of the enteric formulation in the acidic stage was <10% of the loaded FF, whereas that in the phosphate buffer stage was >80%. Pharmacokinetic evaluations in swine revealed that the enteric formulation had a longer t1/2λ and MRT than commercially available FF powder (FULAIKA® ), indicating that the novel formulation exhibited enteric and sustained release properties. Compared with the commercial product, the relative bioavailability of the enteric formulation reached up to 117.2%. This study suggests that this formulation may have potential for future commercialization.

Diffusion-limited PBPK model for predicting pulmonary pharmacokinetics of florfenicol in pig.

For most bacterial lung infections, the concentration of unbound antimicrobial agent in lung interstitial fluid has been thought to be responsible for antimicrobial efficacy. In this study, a diffusion-limited physiologically based pharmacokinetic (PBPK) model was developed to predict the pulmonary pharmacokinetics of florfenicol (FF) in pigs. The model included separate compartments corresponding to blood, diffusion-limited lung, flow-limited muscle, liver, and kidney and an extra compartment representing the remaining carcass. The absorption rate constant and renal and hepatic clearance of FF were determined in vivo. Other parameters were taken from the literature or optimized based on existing pharmacokinetic data. All mathematical operations during the development of the model were performed using acslXtreme version 3.0.2.1 (Aegis Technologies Group, Inc., Huntsville, AL, USA). The model accurately predicted the concentration-time courses of FF in lung interstitial fluid, serum, and plasma following different dosing schedules, except at the dose of 15 mg/kg. When compared with the tissue residue data, the model generally underestimated the FF concentration at the injection site, whereas it gave good predictions of FF concentrations in lung, liver, and kidney at early time points. The model predictions provide a scientific basis for the dosage regimen design of FF.

Nanoemulsion formulation of florfenicol improves bioavailability in pigs.

Nanotechnology applications in medicine have seen a tremendous growth in the past decade and are being employed to enhance the stability and bioavailability of lipophilic substances, such as florfenicol. This study aimed to examine the pharmacokinetic properties of the formulated oil-in-water florfenicol-loaded nanoemulsion (FF-NE). FF-NE and florfenicol control (Nuflor) were administered to the pigs at a dose of 20 mg/kg. Nanoemulsion formulation of florfenicol was highly influenced in vivo plasma profile. The in vivo absorption study in pigs indicated that Cmax (14.54 µg/mL) was significantly higher in FF-NE, 3.42 times higher than the marketed formulation. In comparison with the control group, the relative bioavailability of formulated nanoemulsion was up to 134.5%. Assessment of bioequivalence using log-transformed data showed that the 90% confidence intervals (90% CI) of Cmax and AUC0-∞ were 2.48-4.60 and 1.21-1.72, respectively.

The acute phase response induced by Escherichia coli lipopolysaccharide modifies the pharmacokinetics and metabolism of florfenicol in rabbits.

The aim of this study was to determine the effect of Escherichia coli lipopolysaccharide (LPS)-induced acute phase response (APR) on the pharmaco-kinetics and biotransformation of florfenicol (FFC) in rabbits. Six rabbits (3.0 ± 0.08 kg body weight (bw)) were distributed through a crossover design with 4 weeks of washout period. Pairs of rabbits similar in bw and sex were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 µg/kg bw of E. coli LPS at intervals of 6 h, and Group 2 (control) was treated with an equivalent volume of saline solution (SS) at the same intervals and frequency of Group 1. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples were collected from the auricular vein before drug administration and at different times between 0.05 and 24.0 h after treatment. FFC and florfenicol-amine (FFC-a) were extracted from the plasma, and their concentrations were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using the paired Student t-test. The mean values of AUC0-∞ in the endotoxaemic rabbits (26.3 ± 2.7 µg·h/mL) were significantly higher (P < 0.05) than values observed in healthy rabbits (17.2 ± 0.97 µg·h/mL). The total mean plasma clearance (CLT ) decreased from 1228 ± 107.5 mL·h/kg in the control group to 806.4 ± 91.4 mL·h/kg in the LPS-treated rabbits. A significant increase (P < 0.05) in the half-life of elimination was observed in the endotoxaemic rabbits (5.59 ± 1.14 h) compared to the values observed in healthy animals (3.44 ± 0.57 h). In conclusion, the administration of repeated doses of 1 µg/kg E. coli LPS induced an APR in rabbits, producing significant modifications in plasma concentrations of FFC leading to increases in the AUC, terminal half-life and mean residence time (MRT), but a significant decrease in CLT of the drug. As a consequence of the APR induced by LPS, there was a reduction in the metabolic conversion of FFC to their metabolite FFC-a in the liver, suggesting that the mediators released during the APR induced significant inhibitory effects on the hepatic drug-metabolizing enzymes.

Study of pharmacokinetics of an in situ forming gel system for controlled delivery of florfenicol in pigs.

To reduce florfenicol (FFC) administration frequency in veterinary use, the drug was currently developed into in situ forming gel. Twelve pigs were randomly divided into two groups (six pigs per group). A single i.m. dose of 40 mg/kg body weight (b.w.) was given to pigs, group one was given FFC in situ forming gel, and group two was given FFC conventional injection. High-performance liquid chromatography (HPLC) was used to determine FFC plasma concentrations. There were significant differences (P < 0.01) between FFC in situ forming gel and conventional injection, in pharmacokinetic parameters MRT (mean retention time) (57.79 ± 2.88) h versus (15.94 ± 1.29) h, AUC (area under the concentration-time curve) (421.54 ± 8.97) µg·h/mL versus (168.16 ± 4.59) µg·h/mL, tmax (time of occurrence of cmax ) (9.00 ± 2.68) h versus (4.33 ± 0.82) h, cmax (maximum plasma concentration) (6.87 ± 0.66) µg/mL versus (12.01 ± 0.66) µg/mL, t1/2λz (terminal elimination half-life) (38.04 ± 2.20) h versus (9.15 ± 2.71) h. The results demonstrated that the in situ forming gel system could shorten dosing interval of FFC and thus achieved less frequent administration during long-term treatment.

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep.

Experiments in different animal species have shown that febrile conditions, induced by Escherichia coli lipopolysaccharide (LPS), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS-induced acute-phase response (APR) model on plasma pharmacokinetics of florfenicol (FFC) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 µg/kg bw of E. coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution (SS) at similar intervals as LPS. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann-Whitney U-test. The mean values of AUC0-∞ in the endotoxaemic sheep (105.9 ± 14.3 µg·h/mL) were significantly higher (P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 µg·h/mL). The total mean plasma clearance (CLT ) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS-treated sheep. A significant increase (P < 0.05) in the terminal half-life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E. coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the drug.

A new rotating-disk sorptive extraction mode, with a copolymer of divinylbenzene and N-vinylpyrrolidone trapped in the cavity of the disk, used for determination of florfenicol residues in porcine plasma.

A novel extraction approach was developed based on rotating-disk sorptive extraction (RDSE). In this approach the rotating-disk extraction device consists of a Teflon disk, with a cavity that is loaded with a commercial sorbent phase selected according to the polarity of the analyte. To avoid leakage of the sorbent, the cavity is covered with a fiberglass filter and sealed with a Teflon ring. The proposed novel analytical RDSE technique was used in this study to determine florfenicol levels in plasma as a model analyte, or sample system, to describe the pharmacokinetics of a veterinary formulation. The sorbent used for this application was the copolymer of divinylbenzene and N-vinylpyrrolidone (Oasis HLB), which was selected because the florfenicol molecule contains both hydrophilic and lipophilic moieties. After the extraction, final determination of the analyte was performed by HPLC-DAD. Calibration plots and other analytical features were obtained after 90 min of extraction. The calibration plot was linear over the interval 0.4-16 µg mL(-1) (n = 6), with R (2) = 0.9999. Recovery and repeatability were determined using a blank plasma sample spiked with 4.8 µg mL(-1) florfenicol. A recovery of 91.5 %, with a relative standard deviation (RSD) of 8.8 %, was obtained when the extraction was evaluated using six different rotating-disk devices. Precision was also assessed, using the same disk (containing the same sorbent phase) for eight aliquots of the same sample. The RSD under these conditions was 10.2 %, clearly indicating that the sorptive phase could possibly be re-used. Accordingly, RDSE is a suitable sample preparation alternative to liquid-liquid extraction (LLE), solid-phase extraction (SPE), and stir-bar sorptive extraction (SBSE).

Clinical efficacy of florfenicol administered in the drinking water against Ornithobacterium rhinotracheale in turkeys housed in different environmental conditions: a pharmacokinetic/pharmacodynamic approach.

In poultry rearing, medicated drinking water is a commonly used administration route, but drug uptake can be affected by many factors. In this study, the influence of two important parameters, the photoperiod and feeding schemes, on florfenicol uptake in turkeys was tested. First, the uptake was determined as the pharmacokinetic/pharmacodynamic profile of florfenicol; and second, we evaluated the clinical efficacy of florfenicol against Ornithobacterium rhinotracheale. Both experiments were conducted during a 5-day treatment of 30 mg/kg body weight florfenicol administered via drinking water and considering different photoperiods and feeding schemes (group 20/4L: photoperiod of 20 h, fed ad libitum; group 16/8L: photoperiod of 16 h, fed ad libitum; group 16/8R: photoperiod of 16 h, fed ad libitum but feed was withdrawn during the dark period and replaced 1 h after lighting). On day 1 of treatment, all groups showed plasma concentrations above the minimum inhibitory concentration (both MIC50 and MIC90, 1 mg/l) of 37.7%, 63.5% and 53.1% of a 24-h interval for 20/4L, 16/8L and 16/8R, respectively. Only in the 16/8L and 16/8R groups was the MIC also exceeded on day 5 (47.9% and 21.5% of a 24-h interval, respectively). In all groups, a clinical improvement could be noticed, resulting in reduction of the clinical score. However, only the 16/8L and 16/8R groups showed significant differences from the control group. The results demonstrated an important influence of the photoperiod on the pharmacokinetics of florfenicol as well as the clinical outcome in an infection model. It can be advised that the photoperiod should be <20 h to have sufficient drug intake. Nevertheless, there was no effect between fed and fasted turkeys for both the pharmacokinetics and the clinical outcome.

Multidose pharmacokinetics of orally administered florfenicol in the channel catfish (Ictalurus punctatus).

Plasma disposition of florfenicol in channel catfish was investigated after an oral multidose (10 mg/kg for 10 days) administration in freshwater at water temperatures ranging from 24.7 to 25.9 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After the administration of florfenicol, the mean terminal half-life (t(1/2)), maximum concentration at steady-state (Css (max)), time of Css (max) (T(max)), minimal concentration at steady-state (Css (min)), and Vc /F were 9.0 h, 9.72 µg/mL, 8 h, 2.53 µg/mL, and 0.653 L/kg, respectively. These results suggest that florfenicol administered orally at 10 mg/kg body weight for 10 days could be expected to control catfish bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of <2.5 µg/mL.