Pharmacokinetics And Residues Of Danofloxacin Mesylate In Goldfish (Carassius Auratus)

The plasma pharmacokinetics and tissue residues of danofloxacin mesylate (DFM) were investigated in goldfish {Carassius auratus), under experimental field conditions at 20 ℃, after single oral gavage administration(10 mg/kg b.w). Plasma and tissues samples were collected at different intervals after adiministation of DFM. The samples were determined by using reversed-phase high performance liquid chromatography (RP-HPLC) after liquid-liquid extraction. Ofloxacin hydrochloride was selected as internal standard. The concentration-time data of DFM in plasma were analyzed with 3P97 computer program. The eliminated equation of DFM in tissues were calculated by Statistics Analysis System(SAS). The correlation of calibration curve were all good,which correlation coefficient were more than 0.9990. The limits of detection (LOD) were 0.01 μg/ml, 0.01 μg/g, 0.01 μg/g, 0.02 μg/g, 0.05 μg/g in plasma, muscle, skin, liver, kidney, respectively. The average extraction recovery was more than 69% from skin and more than 78% from other tissues and plasma. The intra-day coefficient of variations and inter-day coefficient of variations were less than 10 %, 15% respectively.Following single oral administration, the plasma concentration-time data of DFM were best described by a two-compartmental open model with absorption, distribution and elimination half-lives of 0.63h, 4.96h, 47.79 h, respectively. The time to peak plasma concentration, Tp, was 2.73 h and peak concentration (C_max) was 3.23 μg/ml. Area under the plasma drug concentration-time curve from 0 to ∞ was 154 μg.h/ml. The mean residence time (MRT) was 58.56 h using non-compartmental anlysis based on statistical moment theory. The eliminated equation in tissues were as follows: C_liver=9.2961e~-0.0157t, C_kidney=19.3019e~-0.02090t, C_muscle= 8.3603e~-0.0136t, C_skin= 2.8624e~-0.0039t, and correlation exponential were 0.93,0.98,0.94,0.72, respectively.Pharmacokinetic analysis of the plasma concentrations showed that DFM exhibited an rapid absorption and distribution, but slow elimination. The results of residues analyses indicated that DFM can penetrate through tissues extensively. The concentratin of DFM in liver, kidney, muscle, skin was significantly higher than in plasma. Theelimination half-lives of drug in liver, kidney, plasma, muscle and skin were 44 h, 33 h, 48 h, 51 h, 177 h, respectively. The concentrations of DFM were highest in liver and kidney. DFM concentration was 1.99±0.32 ug/g in skin at 120 h after oral administration and the DFM concentration was 1.72±0.31 ug/g in the skin, 0.70±0.32 ug/g in the muscle at 168 h after oral administration. Comparing with other tissues, the elimination of DFM in skin was slowest, which behaved as a reservoir tissues in goldfish. It was proposed that withdrawl period should not be less than 23 days after single oral administration of DFM in goldfish at 20 °C, according to the maximum residue limit of 100 ng/kg with 95% confidence for skin. The result also showed that no metabolites of danofloxacin existed in plasma, muscle, skin, liver.