甲磺酸达氟沙星在鲫体内药物动力学及残留研究  

Pharmacokinetics and Residues of Danofloxacin Mesylate in Goldfish (Carassius auratus Linnaeus)

作　　者：潘玉善[1] 操继跃[1] 方之平[1] 王翔凌[1] 潘黔生[2] 丁方科[1] 葛建[1] 彭玉芬[1] 

机构地区：[1]华中农业大学动物医学院,武汉430070 [2]华中农业大学水产学院,武汉430070

出　　处：《中国农业科学》2006年第2期418-424,共7页Scientia Agricultura Sinica

基　　金：国家自然科学基金资助(30271013)

摘　　要：【目的】研究甲磺酸达氟沙星(Danofloxacinmesylate,DFM)在鲫体内的药物动力学和残留消除规律。【方法】在试验水温20℃时,鲫以10mg·kg-1b.w的剂量单次经口灌服甲磺酸达氟沙星后,用液-液提取、反相高效液相色谱法(RP-HPLC)测定血浆和组织中DFM的浓度。盐酸氧氟沙星做为内标。房室模型分析表明,其药物时间数据符合有吸收二室模型,吸收、分布迅速,但消除缓慢,半衰期(T1/2Ka、T1/2α、T1/2β)分别为0.63、4.96、47.79h,最大血药浓度(Cmax)为3.23μg·ml-1,达峰时间(TP)为2.73h,药时曲线下面积(AUC)为154μg·h·ml-1。非房室模型分析表明,平均滞留时间(MeanResidenceTime,MRT)为58.56h。【结果】组织中药物浓度在测定时间里均显著高于血浆(P<s0.05),消除快慢依次为肾脏、肝胰脏、血浆、肌肉和皮肤,其消除半衰期分别为33、44、48、51、177h。与其它组织相比皮肤消除最慢,建议其作为DFM在鲫体内的残留靶组织。在20℃时,皮肤以100μg·kg-1为最高残留限量(maximumresiduelimit,MRL)建议休药期不低于23d。[Objective and method] The plasma pharmacokinetics and tissue residues of danofloxacin mesylate （DFM） were investigated in goldfish, under experimental field conditions at 20℃ after single oral gavage administration（10 mg.kg^-1 b.w）. The danofloxacin concentrations in plasma and tissues samples were determined by using reversed-phase high performance liquid chromatography （RP-HPLC） after liquid-liquid extraction. Ofloxacin hydrochloride was selected as internal standard. Plasma concentration-time data of DFM were best fitted using a two-compartmental open model, with absorption, distribution and elimination half-life of 0.63, 4.96 and 47.79 h, respectively. The maximal plasma concentration was 3.23 lag-mll, peaking at 2.73 h after dosing. Area under the plasma drug concentration-time curve from 0 to ∞ was 154μg.h.ml^-1. The mean residence time （MRT） was 58.56 h using non-compartmental analysis based on statistical moment theory. [Results] The results indicated that the concentration of DFM in kidney, liver, plasma, muscle and skin was significantly higher than that in plasma, with elimination half-life of 33, 44, 48, 51 and 177 h, respectively. To compare with other tissues, the elimination of DFM in skin was slowest, which behaved as a reservoir tissues in goldfish. It is proposed that withdrawl period should be not less than 23 days after single oral administration （10 mg.kg^-1.bw） of DMF to goldfish at 20℃, according to the maximum residue limit（MRL） of 100 mg·kg^-1 in skin.

关 键 词：鲫 甲磺酸达氟沙星 药物动力学 休药期 

分 类 号：S948[农业科学—水产养殖]