Studies On Pharmacokinetics And Tissue Residues Of Sarafloxacin Hydrochloride In Goldfish (Carassius Auratus)

This study developed a method to detect sarafloxacin in goldfish plasma and tissues using reverse phase high performance liquid chromatorgraphic method (RP-HPLC). Pharmacokinetics and residues of sarafloxacin hydrochloride were investigated, following single oral administration at dose of 20mg/kgb · w in healthy female goldfish (Carassius auratus). 90 female goldfish were randomly divided into 18 groups for the experiments. The plasma and five tissues (muscle, skin, hepatopancreas, kidney, ovary) were collected at different intervals after administration of sarafloxacin hydrochloride. Danofloxacin mesylate was used as inner standard and dichloromet- hane was used as extractant. The extracts were evaporated to dryness by N₂ flow at water bath of 60℃ and were dissolved in mobile phase. Then the fat of the solute was degreased was by hexane and analysed by RP-HPLC. The mobile phase was acetonitrile and 0.2mol/L phosphate buffer (pH 7.4) (including 0.5% tetrabutyl ammonium bromide) (10/90, V/V) adjusted to pH 3.0 with phosphoric acid. Sarafloxacin hydrochloride and danofloxacin mesylate were quantitated by using ZORBAX SB-C₁₈ column and ultraviolet detector was set at 280nm. The mean recoveries for all samples were all exceed 82.97%, Intra-day CV and inter-day CV are under 6.04% and 7.11% respectively. Both LOD and LOQ can meet the requirement of the residual detection.The concentration-time data of sarafloxacin hydrochloride in plasma of healthy female goldfish after single oral administration was fitted to two-compartment model with first order absorption. The pharmacokinetic equation was : C_plasma=l.28e^-0.26t +0.31e^-0.01t-1.59e^-4.46t. The main pharmacokinetic parameters for plasma were: distribution half- life (t_1/2α), absorption half-life (t_1/2ka) and elimination half-life (t_1/2β) were 2.72 h, 0.16 h, 67.97h respectively. The area under the curve (AUC), the time to peak concentration and the peak concentration were 35.25μg · mL^-1 · h, 0.72h and1.3 l^fg/mL respectively. After single oral administration of sarafloxacin hydrochloride to healthy female goldfish, the concentration-time data of sarafloxacin hydrochloride in muscle, skin and ovary were best described by biexponential equations, while those in hepatopancreas and kidney were best described by triexponential equations. The pharmacyokinetic equations were shown as follow:n c? /_.-0.03t -0.11K. r> 1 /-o/- -O.Olt a-0.24tvr. - ^<sup>, -0.02t -0.51(xCmuSc!e= 5.35 (e -e ); Cskin=1.69(e -e );COVary=3.32(e -e );r -rx-i {.no-0-231 a. a ziR^-003' 40 n?p-°-37t ? r -1 ^ ii<.-oo8ij.<;C hepatopancreas =â– $ I-OVC + 4.48e - 4Z.Ube , Ckidney=l^>-lle +5.20.79e'°22t. The main pharmacokinetic parameters for muscle were ti/2ka 6.16h, elimination half-life(t1/2ke)27.49h, Tmax 17.18h, Cmax 2.69/ig/g, AUC 164.44fig-g'1 -h; The main pharmacokinetic parameters for skin were ty2ka2.87h, tj/2ke 51.74h, Tmax 12.68h, Cmax l-35^g/g, AUC 119.18/ig ? g"1 ? h; The main pharmacokinetic parameters for ovary were ti/2ka l-36h, t1/2ke 36.24h, Tmax 6.68h, Cmax 2.81fig/g, AUC 167.16 jug â–  g"1 ? h; The main pharmacokinetic parameters for hepatopancreas were ti/2<. 2.96h, ti^ 24.37h, ti/2ka 1.90h, Tmax 4.04h, Cmax 8.97^g/g, AUC 202.91 fig ? g1 - h. The main pharmacokinetic parameters for kidney were ti/2? 8.47h, ti/2? 61.50h, ti/2ka 3.11h, Tmax 8.74h, Cmax 9.58/ig/g, AUC 595.43^g -g'1 -h. The elimination equations for tissues were as follows: CmUscie=4.38e"a02l;CSkin=1.82e"0'011; C hepatopancreas =5.65e-003t;f ' Q 1A -°-02t. p _i (yj _-0.02t^=-'-'^e ', COvary—" FThe results showed that the pharmacokinetic character of sarafloxacin hydrochloride in plasma of healthy female goldfish was as follows: Sarafloxacin hydrochloride was absorbed fast and the time to peak concentration was short. The drug was slowly eliminated after a single oral aministration in healthy goldfish. The pharmacokinetic character of tissues were as follows: Sarafloxacin hydrochloride concentration were high and distributed extensively in goldfish. The penetration into tissues was strong and this drug could be effective in the treatment of whole body and deep tissues infections in goldfish. The character of residue and elimination was both residual quantity of sarafloxacin hydrochloride and elimination rate were different significantly in every tissues. The concentration of sarafloxacin hydrochloride in kidney and hepatopancreas was more higher than other tissues and skin showed the slowest depletion among five tissues, The target tissue of residue was kidney. From the formula of withdrawl period , It was suggested that the withdrawl period shouldnot be less than 14 days after single oral administration of sarafloxacin hydrochloride in healthy female goldfish.