恩诺沙星及其代谢产物环丙沙星在拟穴青蟹体内的药代动力学  

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in mud crab(Scylla paramamosain)

作　　者：周帅[1] 胡琳琳[1] 房文红[1] 周凯[1] 于慧娟[1] 

机构地区：[1]中国水产科学研究院东海水产研究所,农业部海洋与河口渔业资源及生态重点开放实验室,上海,上海200090

出　　处：《水产学报》2011年第8期1182-1190,共9页Journal of Fisheries of China

基　　金：中央级公益性科研院所基本科研业务费专项资金(中国水产科学研究院东海水产研究所2007M06);上海市科技兴农推广项目[沪农科推字(2008)第2-1号]

摘　　要：采用高效液相色谱法,研究盐度33条件下恩诺沙星口灌和肌肉注射给药(剂量10 mg/kg)后,恩诺沙星及其代谢物环丙沙星在拟穴青蟹体内的药代动力学和组织分布。血淋巴和组织中药代动力学参数采用基于统计矩原理的非房室模型进行计算。恩诺沙星口灌和肌肉注射拟穴青蟹给药后,血药达峰快,分别为0.5 h和1 min,达峰浓度分别为12.90和31.86μg/mL,曲线下面积(AUC)分别为216.1和816.8μg/(mL.h)。恩诺沙星在拟穴青蟹组织中分布较广,口灌给药下肌肉和肝胰腺AUC分别为445.9和817.6μg/(g.h),肌肉注射给药下的AUC分别为554.7和2 573.7μg/(g.h)。与其它水产动物相比,恩诺沙星在拟穴青蟹体内消除速度为中等水平,口灌和肌肉注射恩诺沙星后血药消除半衰期(t1/2z)分别为26.45和57.02 h,总体清除率(CLz)分别为0.054和0.012 L/(h.kg)。恩诺沙星在拟穴青蟹体内代谢生成环丙沙星的量较少,口灌给药下血淋巴、肌肉和肝胰腺的AUCCIP/AUCENR分别为6.66%、3.66%和4.78%,肌肉注射给药下,其相应值分别为4.16%、7.24%和1.48%,在拟穴青蟹体内起药效作用仍是以恩诺沙星为主。以Cmax/MIC、AUC0-24/MIC评价恩诺沙星在青蟹体内的药效作用,建议给拟穴青蟹以10 mg/kg剂量每隔24小时投喂一次恩诺沙星,对弧菌引起的细菌性疾病具有较好的防治效果。The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin were investigated in the mud crab（Scylla paramamosain）kept at a salinity of 33 after a single oral gavage and intramuscular injection（10 mg/kg）.The concentrations of enrofloxacin and ciprofloxacin in the main tissues（hemolymph,muscle and hepatopancreas）were simultaneously detected by HPLC.The parameters in hemolymph and tissues were calculated by non-compartment model based on statistic moment theory.The peak plasma enrofloxacin was fast reached after oral gavage and intramuscular injection.The peak time were 0.5 h and 1 min for oral gavage and intramuscular injection,respectively and the peak concentration of enrofloxacin was 12.90 and 31.86 μg/mL,respectively.Area under the concentration-time curve（AUC）in hemolymph was 216.1 and 816.8 μg/（mL·h）,respectively.Enrofloxacin was widely distributed in mud crab tissues.AUC of muscle and hepatopancreas were 445.9 and 817.6 μg/（g·h）,respectively,following oral gavage and AUC of muscle and hepatopancreas were 554.7 and 2 573.7 μg/（g·h）,respectively,after intramuscular injection.Compared with other aquatic animals,enrofloxacin was eliminated at a medium level.Half-life of elimination（t1/2z）and body clearance（CLz）were 26.45 h and 0.054 L/（h·kg）,respectively,for oral gavage,and 57.02 h and 0.012 L/（h·kg）,respectively,for intramuscular injection.The AUC ratios of ciprofloxacin and enrofloxacin in mud crab hemolymph,muscle and hepatopancreas were 6.68%,3.60% and 4.78%,respectively,following oral gavage,and the corresponding values were 4.16%,7.24% and 1.48%,respectively,after intramuscular injection.Enrofloxacin in mud crab metabolized less ciprofloxacin and enrofloxacin played a main role in the efficacy in the mud crab.The efficacy of enrofloxacin in mud crab was evaluated with Cmax/MIC ratio and AUC0-24/MIC ratio.Oral gavage of enrofloxacin at a single dosage of 10 mg/kg once every 24 h could yield good therapeutic efficacy on vibrio diseases.

关 键 词：拟穴青蟹 恩诺沙星 代谢产物环丙沙星 口灌给药 肌肉注射给药 药代动力学 

分 类 号：R969.1[医药卫生—药理学] S917.4[医药卫生—药学]