Studies On The Pharmacokinetics And The Elimination Regularity Of Florfenicol Residues In Paralichthys Oliuaceus (T&S) In Vivo

Florfenicol as single- fluoride Thiamphenicol derivatives is a new generation of chloramphenicol veterinary synthetic antibiotics. Mechanism of the drug is the same as chloramphenicol, but antibacterial activity is better than thiamphenicol and chloramphenicol. Since the 1990 s, because of its broad-spectrum,highly efficiency,rapid absorption,extensive tissue distribution,safety,animal-specific and low incidence of resistance, FFC has been used widly in stockbreeding and aquaticulture at home and abroad. Therefore, Understanding and mastering the pharmacokinetics and the elimination regularity of florfenicol residues in the flounder in vivo provides an important scientific and guiding significance for its application of aquaculture in China.In this paper, first of all, a High Performance Liquid Chromatography (HPLC) for FFC in the flounder in vivo analysis is optimized though comparing the relational researches. The florfenicol residues are extracted from tissues by Ethyl Acetate. After homogeneity and centrifuge,the solution is treated with n-hexane to remove the fat. The extract is evaporated and the residue is dissolved by phosphate, then dissolved liquid is filtered with 0.22μm membrane followed by HPLC. Chromatogram condition is: column, ODS– C 18 (250 mm×4.6 mm, Filler particle size 5μm); mobile phase, V (CH3CN): V (H2O) = 30: 70; column temperature, 35℃; flow-rate, 0.75 mL·min^-1; injection volume is 20μL; detectors, (VWD); UV detection wavelength, 224 nm (External standard for quantification). After fortified at different levels, average recoveries of FFC are between 86.83 % 103.30 %. The relative standard deviations are all lower than 10 %. The detection limit is 0.05μg·mL^-1. Chromatographic conditions can fulfil detection needs.We divide the flounder (average weight: 200 g) into three groups: the dose of 50 mg·kg^-1 weight of FFC after oral administration for five consecutive days,the dose of 80 mg·kg^-1 weight of FFC after single oral administration and the dose of 10 mg·kg^-1 weight of FFC after IM injection. The concentrations of florfenicol are determined by High Performance Liquid Chromatography, The concentration-time data derived from the experiment is processed with origin 7.5, the data of single oral administration and IM injection are analyzed by pharmacokinetics software DAS 2.1.1 to derive pharmacokinetic parameter values, and then summarize the pharmacokinetics and the elimination regularity of florfenicol residues in the flounder in vivo. In this paper, the pharmacokinetics and the elimination regularity of florfenicol residues in the flounder in vivo are firstly studied. The results indicate that:1. The dose of 50 mg·kg^-1 weight of FFC after oral administration for five consecutive days, the first day, florfenicol concentration in the muscles is significantly lower than the liver, kidney and blood. After ten days, the muscle and the blood have similar residual regularity,small residues relatively, and the faster elimination rate than liver. Comparative studies show that the concentration of florfenicol in the flounder has faster elimination rate than other antibacterial drugs quickly. When the concentration of edible tissue of florfenicol reaches 0.1μg·g^-1, in this culture environment, the temperature in the process of breeding is 16 18℃, we suggest that the off-drug period is more than 18 days (Product of temperature and time is not less than 324).2. The dose of 80 mg·kg^-1 weight of FFC after single oral administration, concentration-time curves of florfenicol can be seen that the muscles and liver peak in the fastest growing speed (Tmax is 1 hour), and Tmax in the blood is 2 hours (referred to as 2 h). The florfenicol residues are the highest in the liver, the lowest in the blood, and florfenicol in the muscle after 384 h (16 days) has been not detected. Under the conditions of this experiment, florfenicol in the flounder in vivo has rapid absorption and wide distribution, but when the concentration reaches 0.1μg·g-1, we suggest that the off-drug period is more than 16 days (the product of temperature and time is not less than 288).3. The dose of 10 mg·kg^-1 weight of FFC after IM injection, liver is peak time (Tmax) for 10 h, blood and muscle are the peak for 6 h. Blood,muscle and liver at concentrations-time area under the curve (AUC) are 218.024 mg / L·h, 76.309 mg / L·h and 183.943 mg / L·h, and steady-state apparent volume[V_z/F] is greater than one that shows Florfenicol is distributed widely in the body, high concentrations of drug in the organizations.Tests show florfenicol residues in the liver of the flounder in vivo are higher than the blood and muscle, which is accord with the relational reports. So the liver of animals is the main organ of drug metabolism, and the edible muscle tissue has a relatively small residue. Florfenicol administration in three different ways, oral administration is better than injection, but oral administration dosen't facilitate the quantitative, especially one-time administration.Because of different absorption in individual animals , it can select appropriate delivery methods according to the actual situation.