诺氟沙星在大黄鱼体内的药代动力学及残留研究
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国家“十五”渔业科技攻关计划项目


Pharmacokinetics and residues of norfloxacin in Pseudosciaena polyactis
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    摘要:

    在试验水温(22±2) ℃时,按10 mg/kg的剂量给大黄鱼单次口服诺氟沙星后,用高效液相色谱法测定血浆和组织中的药物浓度,研究了诺氟沙星在大黄鱼体内的代谢及消除。结果表明血药时间数据符合一级吸收二室开放模型,吸收分布迅速,但消除缓慢,半衰期(T1/2 Ka、T1/2α、T1/2β)分别为0.703 0、2.092 6、154.326 5 h,最大血药浓度为0.886 4 μg/mL,达峰时间为2.091 4 h,药时曲线下面积(AUC)为97.803 8 μg/h·mL。组织中肝脏的药物浓度最高,在测定的时间里各组织的药物浓度高于血浆。药物消除速度依次为:肾脏、肝脏、肌肉,消除半衰期分别为135.88、173.25、223.55 h,肌肉作为可食性组织,且消除最慢,因此选取肌肉组织作为残留检测的靶组织,以50 μg/kg为最高残留限量,因此在本试验条件下,建议休药期不低于23 d;在治疗大黄鱼细菌性疾病时,以诺氟沙星10 mg/kg剂量给药,一般1 d 1次,连用2~3 d

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    In order to study the metabolism and elimination of norfloxacin (NFLX) in Pseudosciaena polyactis, single oral administration(10 mg/kg b.w) of NFLX has been investigated in healthy Pseudosciaena polyactis at (22±2) ℃. The medicine was extracted by methanol from plasma and perchloric acid (6%) from tissues. NFLX was determined by high performance liquid chromatography(HPLC). The mobile phase was methanol, 0.05 mol/L phosphate buffer and 0.05 mol/L terabutyl ammonium bromide (24.5/73.5/2, V/V/V) adjusted to pH 2.0 with phosphoric acid. The ZORAX SBC18 column was used and ultraviolet detector was 280 nm. The mean recoveries were all higher than 88.73% for samples and interday CV for plasma and tissues were all under 9.75 %. The sensitivity was 0.01 μg/mL. The result demonstrated: Plasma concentrationtime data of NFLX were best fitted using a twocompartmental open model, absorption and distribution were fast but elimination was slow, with absorption, distribution and elimination halflife of 0.703 0, 2.092 6 and 154.326 5 h, respectively. The maximal plasma concentration was 0.886 4 μg/mL, peaking at 2.091 4 h after dosing. Area under the plasma drug concentrationtime curve from 0 to ∞ was 97.803 8 μg/h·mL. The concentration of NFLX was higher than other tisssues and all tissues’ concentration is higher than plasma at the same time. The speed from fast to slow is kidney, liver, muscle with elimination halflife of 135.88,173.25,223.55 h, respectively. As an edible tissue, muscle had a slowest depletion, so muscle was selected as target tissue in this experiment. According to the maximum residue limit(MRL) of 50 μg/kg in muscle, the withdrawl period should not be less than 23 d under this experiment condition; then the scheme of NFLX is established to fish bacterial disease, that is,the dose orally is l0 mg/kg, at the intervals of 24 h for 2~3 times.This study had theory value to application of norfloxacin (NFLX) to disease prevention and cure for aquatic animals and consumer’s health safety.

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刘玉林.诺氟沙星在大黄鱼体内的药代动力学及残留研究[J].水产学报,2007,31(5):655~660

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  • 收稿日期:2007-09-04
  • 最后修改日期:2007-09-04
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  • 在线发布日期: 2007-09-05
  • 出版日期: 2007-09-15
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