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机构地区:[1]上海海洋大学水产与生命学院,国家水生动物病原库,农业部淡水种质资源重点实验室,上海201306
出 处:《西北农林科技大学学报(自然科学版)》2016年第6期46-52,共7页Journal of Northwest A&F University(Natural Science Edition)
基 金:农业部现代农业产业技术体系建设专项(CARS-46-12)
摘 要:【目的】研究盐酸沙拉沙星在鲫鱼体内的药代学、药效动力学联合参数,确定盐酸沙拉沙星治疗鲫鱼细菌性疾病的防耐药突变用药方案。[方法】测定盐酸沙拉沙星对嗜水气单胞菌的体外最小抑菌浓度(MIC)、最小杀菌浓度(MBC)、抗菌后效应(PAE)、防耐药突变浓度(MPC)和防耐药突变选择窗(MSW);给鲫经口灌服不同剂量(20,30,40mg/kg)的盐酸沙拉沙星,于给药后0.5,1,2,4,6,8,10,12,16,24,48h取血清及肌肉样品,研究盐酸沙拉沙星在鲫鱼体内的药代动力学,然后结合药代动力学和药效动力学结果,确定盐酸沙拉沙星防治嗜水气单胞菌引起的鲫鱼细菌性败血症的合理给药方案。【结果】盐酸沙拉沙星对嗜水气单胞菌的MIC为0.5μg/mL,MBC为2.Oμg/mL,MPC为2.5μg/mL,MSW为0.5-2.5μg/mL。按20,30,40mg/kg剂量给鲫鱼经口灌服盐酸沙拉沙星后,鲫鱼体内的血药质量浓度大于MPC的维持时间分别为0,4.0,24.0h;AUC24/MIC分别为8.44,78.20,164.96;Cmax/MIC分别为4.496,6.662,15.294。【结论】40mg/kg灌服剂量能使鲫的血药浓度维持在MPC以上的时间≥(24一PAE)h、AUC24/MIC≥100或Cmax/MIC〉8,因此建议盐酸沙拉沙星防治嗜水气单胞菌引起的鲫鱼细菌性败血症的防突变用药方案为:给药剂量40mg/kg,每日给药1次,休药期不低于10d。[Objective] This study investigated in vitro pharmacodynamics (PD) parameters and in vivo pharmacokinetics (PK) parameters to determine the rational dosage of Sarafloxacin in crucian carp (Carassius auratus). [Method] The pharmacodynamics of Sarafloxacin on Aeromonas hydrophila were studied in vitro and the parameters were monitored after a single oral gavage of 20,30, and 40 mg per kg body weight to determine a medication regimen to prevent bacterial sepsis in crucian carp. [Result] The minimal inhibitory concentration (MIC) of Sarafloxacin on AH10 was 0.5 μg/mL,the minimum bactericidal concentra- tion (MBC) was 2.0 μg/mL,the mutant prevention concentration (MPC) was 2.5 μg/mL,and the mutant selection window (MSW) for the pathogenic bacterial strains was 0.5-2.5 μg/mL. The time for Saraflox- acin concentration of 〉MPC in serum of crucian carp were 0,4.0,and 24.0 h at the dosages of 20,30,and 40 mg/kg,respectively. The AUC24/MIC values were 8.44,78. 20 and 164. 96, and the Cmax/MIC values were of 4. 496,6. 662,and 15. 294,respectively. [Conclusion] The dosage of 40 mg/kg resulted in MPC≥ (24--PAE) h, AUC24/MIC≥100 or Cmax/MIC〉8. Thus, the applicable regimen for prevention and treatment of bacterial diseases of crucian carp is 40 mg/kg,once per day,and no less than 10 d for withdrawal period.
关 键 词:鲫 盐酸沙拉沙星 防耐药突变浓度 嗜水气单胞菌 药代动力学 药效动力学
分 类 号:S943.117.413[农业科学—水产养殖]
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