鲫细菌性疾病控制中甲砜霉素药代-药效动力学联合参数的研究
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国家水生动物病原库,国家水生动物病原库,国家水生动物病原库,国家水生动物病原库,国家水生动物病原库,国家水生动物病原库,国家水生动物病原库

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现代农业产业技术体系建设专项资金(CARS-46-12)


Integrated pharmacokinetics-pharmacodynamics parameters of thiamphenicol in crucian carp(Carassius auratus)
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National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University,National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University,National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University,National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University,National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University,National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University,National pathogen collection center for aquatic animals,College of Fisheries and Life Science,Shanghai Ocean University

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    摘要:

    采用高效液相色谱法, 研究了甲砜霉素对致病性嗜水气单胞菌AH10(Aeromonas hydrophila)体外药效学参数及口灌不同剂量的甲砜霉素在鲫体内药代动力学特征, 并制定甲砜霉素控制鲫细菌性败血症防耐药突变用药方案。研究结果表明, 甲砜霉素对AH10的最小抑菌浓度(minimal inhibitory concentrations, MIC)为1.0 μg/mL;最小杀菌浓度(minimal bactericidal concentrations, MBC)为2.0 μg/mL;防细菌耐药突变浓度(mutant prevention concentration, MPC)为8.0 μg/mL;防耐药突变选择窗(mutant selection window, MSW)为1.0~8.0 μg/mL。在试验水温(22±1)℃条件下, 对鲫口灌20、30、40 mg/kg体重剂量的甲砜霉素, 24 h内血药浓度大于MPC的维持时间分别为3、8、22 h; AUC24(area under the drug concentration-time curve)/MIC分别为89.539、174.560、251.682; Cmax(maximum concentration in the interval)/MIC分别为14.92、17.69、24.22;。综合血药浓度维持MPC 以上的时间超过24 h、AUC24/MIC>125或Cmax/MIC>10等指标, 建议甲砜霉素控制鲫细菌性败血症的防耐药用药方案为:剂量40 mg/kg, 一日一次。根据肌肉内甲砜霉素的药动学方程, 药残达到国家限量标准所需时间约为15 d, 所以在本试验水温(22±1)℃下, 建议休药期不低于15 d。

    Abstract:

    In this study, the pharmacodynamics (PK) of thiamphenicol on pathogenic Aeromonas hydrophila strain (AH10) and the pharmacokinetic (PD) parameters of thiamphenicol in crucian carp(Carassius auratus)were investigated by high-performance liquid chromatography (HPLC) system, which were used to draw reasonable medication regimen to control disease and prevent drug resistant bacteria. The in vitro pharmacodynamic results showed that the minimal inhibitory concentrations(MIC) of thiamphenicol on AH10 was 1.0 μg/mL, and the minimal bactericidal concentrations (MBC) was 2.0 μg/mL; the mutant prevention concentration (MPC) was 8.0 μg/mL (8MIC); the mutant selection window (MSW) of thiamphenicol on the pathogenic bacterial strains was 1.0-8.0 μg/mL. The time of thiamphenicol concentration in serum of crucian carp above MPC was 3h at the dosage of 20 mg/kg; 8h at the dosage of 30 mg/kg, 22 h at the dosage of 40 mg/kg, respectively;AUC24(Area under the drug concentration-time curve)/MIC and Cmax(Maximum concentration in the interval)/MIC of thiamphenicol in serum were 89.539 and 14.92 at the dosage of 20 mg/kg, respectively; 174.560 and 17.69 at the dosage of 30 mg/kg, respectively; 251.682 and 24.22 at the dosage of 40 mg/kg, respectively. Considering the drug remained in the plasma with a concentration above MPC for 24 h and AUC24/MIC>125 or Cmax/MIC>10, it is suggested that hemorrhagic septicemia can be controlled using a dosing regimen of 40 mg/kg thiamphenicol, at intervals of 24 h. The proposed withdrawal time in crucian carp should not be less than 15 d at the water temperature of (22±1)℃.

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李梦影,喻飞,张国亮,孙朋辉,胡鲲,杨先乐,吕利群.鲫细菌性疾病控制中甲砜霉素药代-药效动力学联合参数的研究[J].上海海洋大学学报,2015,24(4):587-593.
LI Mengying, YU Fei, ZHANG Guoliang, SUN Penghui, HU Kun, YANG Xianle, L&#; Liqun. Integrated pharmacokinetics-pharmacodynamics parameters of thiamphenicol in crucian carp(Carassius auratus)[J]. Journal of Shanghai Ocean University,2015,24(4):587-593.

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  • 收稿日期:2015-01-12
  • 最后修改日期:2015-02-16
  • 录用日期:2015-05-22
  • 在线发布日期: 2015-07-22
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