中国农业科学 ›› 2006, Vol. 39 ›› Issue (02): 418-424 .

• 畜牧·兽医·资源昆虫 • 上一篇    下一篇

甲磺酸达氟沙星在鲫体内药物动力学及残留研究

潘玉善,操继跃,方之平,王翔凌,潘黔生,丁方科,葛健,彭玉芬   

  • 收稿日期:2005-03-15 修回日期:1900-01-01 出版日期:2006-02-10 发布日期:2006-02-10

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

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  • Received:2005-03-15 Revised:1900-01-01 Online:2006-02-10 Published:2006-02-10

摘要: 【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。

关键词: 鲫, 甲磺酸达氟沙星, 药物动力学, 休药期

Abstract: 【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.

Key words: Goldfish (Carassius auratus), Danofloxacin mesylate, Pharmacokinetics, Withdrawal period