药饵投喂下诺氟沙星在凡纳滨对虾主要组织中的分布及消除规律研究

Distribution and Elimination of Norfloxacin in Primary Tissues of Litopenaeus vannamei after Oral Administration

将诺氟沙星原药(98%)按质量比为1:1 000制成颗粒饵料投喂凡纳滨对虾,研究在养殖模式下诺氟沙星在凡纳滨对虾各组织中的分布及消除规律。采用高效液相色谱法结合药代动力学分析软件3P97分析诺氟沙星在凡纳滨对虾体内的药物回收率、动力学参数、药时曲线等参数。结果表明,诺氟沙星血药浓度时间曲线符合吸收二室模型,动力学方程分别为:C血淋巴=9.236 e-0.662 t+56.938 e-0.01 t-66.174 e-0.985 t,C肌肉=21.491 e-0.576 t+0.328 e-0.047 t-21.819 e-0.726 t,C肝胰腺=30 115.96 e-0.355 t+39.314 e-0.01 t-30 155.274 e-0.378 t。血淋巴、肌肉、肝胰腺中诺氟沙星达峰时间Tmax分别为1 h、4 h和4 h,峰浓度值Cmax分别为13.527 5 mg/L、1.904 4 mg/L和698.916 7 mg/L,表观分布容积V1/F分别为0.017 L/kg、0.210 L/kg和0.001 L/kg,吸收半衰期T1/2Ka分别为0.704 h、0.954 h和1.832 h,分布半衰期T1/2α分别为1.047 h、1.204 h和1.951 h,消除半衰期T1/2β分别为69.315 h、14.812 h和69.315 h,中央室向周边室转运的一级速率常数K12分别为4.347 h-1、0.098 h-1和0.098 h-1,周边室向中央室转运的一级速率常数K21分别为0.629 h-1、0.081 h-1和0.017 h-1,药时曲线下面积AUC分别为6.764 mg·h-1·L-1、9.538 mg·h-1·L-1和7013.467 mg·h-1·L-1。血淋巴、肌肉、肝胰腺组织中诺氟沙星浓度水平的结果表明,诺氟沙星在凡纳滨对虾3种组织中浓度最高的为肝胰腺;肌肉和血淋巴中诺氟沙星代谢较快,在投喂8 h后药物残留接近于零,但肝胰腺组织易蓄积诺氟沙星,其残留时间至16 d才未被检测到。实验实施期间为9月份,平均水温为28℃,因此,使用质量比为1:1 000制成颗粒饵料投喂凡纳滨对虾至少应经过448℃.d后才能消除。

The Pellet feed was prepared by using norfloxacin（98%） and shrimp conventional feed with mass ratio of 1：1 000, distribution and elimination of norfloxacin in Litopenaeus vannamei tissues were studied under the culture mode. high performance liquid chromatography（HPLC） was used to determine the recovery rate, kinetic parameters and time curve of norfloxacin in L. vannamei. The data of drug concentration-time were analyzed usi ng pharmacokinetics software 3 P97. The result showed that blood concentration-time data was best fitted using a two-compartment model with first absorption. The pharmacokinetic equations were CHemolymph=9.236 e-0.662 t＋56.938 e-0.01 t-66.174 e-0.985 t, Cmuscle=21.491 e-0.576 t＋0.328 e-0.047 t-21.819 e-0.726 t, CHepatopancreas=30115.96 e-0.355 t＋39.314 e-0.01 t-30 155.274 e-0.378 t. Peak concentrations（Tmax） of norfloxacin inhemolymph, muscle,andhepatopancreas were 13.527 5 mg/L, 1.904 4 mg/L and 698.916 7 mg/L at 1 h, 4 h and 4 h respectively.Distribution volume（V1/F） of norfloxacin inhemolymph, muscle, andhepatopancreas were 0.017 L/kg, 0.210 L/kg and 0.001 L/kg respectively. The absorptionhalf-life（T1/2 Ka） were 0.704 h, 0.954 h, 1.832 h and distributionhalf-life（T1/2α） were 1.047 h, 1.204 h and 1.951 h respectively inhemolymph, muscle, andhepatopancreas respectively. The eliminationhalf-life（T1/2β） of norfloxacin inhemolymph, muscle, andhepatopancreas were 69.315 h, 14.812 h and 69.315 h respectively. First-order rate constants of norfloxacin transporting from central compartment to peripheral compartment（K12） were 4.347 h-1, 0.098 h-1, 0.098 h-1 and transporting from peripheral compartment to central compartment（K21） were 0.629 h-1, 0.081 h-1, 0.017 h-1 inhemolymph, muscle, andhepatopancreas respectively. The areas under the curve（AUC） of norfloxacin were 6.764 mg·h-1·L-1, 9.538 mg·h-1·L-1 and 7013.467 mg·h-1·L-1 in those three tissues. Results of norfloxacin concentrations inhemolymph, muscle,andhepatopancreas of L. vannamei showed that thehighest concentration levels of norfloxacin was inhepatopancreas. Compared tohepatopancreas, norfloxacin metabolized faster in muscle andhemolymph, and the drug residue is close to zero after feeding 8 h. Norfloxacin was easy to accumulate inhepatopancreas, and its residue time was 16 d. The average water temperature was 28 ℃ during the experimental time. So it should at least through 448 ℃.d to eliminate norfloxacin（98%, mass ratio of 1：1 000 with shrimp bait） for L. vannamei.