甲磺酸达氟沙星在鲫体内药物动力学及残留研究

 【目的】研究甲磺酸达氟沙星(Danofloxacin mesylate, 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10 mg·kg-1 b.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（T1/2 Ka 、T1/2α、T1/2β）分别为0.63、4.96、47.79 h，最大血药浓度（Cmax）为3.23 ?g·ml-1，达峰时间（TP）为2.73 h，药时曲线下面积（AUC）为154 ?g·h·ml-1。非房室模型分析表明，平均滞留时间（Mean Residence Time, MRT）为58.56 h。【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、177 h。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100 ?g·kg-1为最高残留限量（maximum residue limit, MRL）建议休药期不低于23 d。

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

【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 μg·ml-1, peaking at 2.73 h after dosing. Area under the plasma drug concentration-time curve from 0 to ∞ was 154 μg·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.