不同温度下复方磺胺嘧啶在罗非鱼体内的药代动力学
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公益性行业(农业)科研专项(201203085);广东省鱼病防治专项资金(2012年)


Pharmacokinetic of compound sulfadiazine in Oreochromis niloticus at different temperatures
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    【目的】探讨不同温度条件下复方磺胺嘧啶在罗非鱼 Oreochromis niloticus 血液中的药代动力学(简称药动学)特点及其变化.【方法】以罗非鱼为研究对象,在不同水温(18、23、28和33 ℃)饲养条件下以复方磺胺嘧啶[m(磺胺嘧啶)∶m(甲氧苄啶)=5∶1]按120 mg/kg的剂量单次饲喂给药,分别于给药后0.5、1、2、4、6、8、10、24、48、72 h采集血液样品,使用HPLC方法检测罗非鱼血浆中的药物质量浓度,研究复方磺胺嘧啶在罗非鱼血液中的吸收和消除变化规律.【结果和结论】18、23、28和33 ℃时,磺胺嘧啶在血浆中的峰质量浓度分别为12.41、19.60、22.48和30.78 μg/mL,甲氧苄啶在血浆中的峰质量浓度分别为1.22、2.06、2.44和2.70 μg/mL,2个药物的峰质量浓度均随着温度的升高而增大.磺胺嘧啶在血浆中的消除半衰期(t1/2 ke)分别为18.22、17.89、16.90和12.99 h,甲氧苄啶在血浆中的 t1/2 ke 分别为16.39、7.08、5.99和4.04 h,药物的消除随温度的升高而加快;各温度下药物在罗非鱼血液中的药动学均为1级动力学过程.给药后10 h内血浆中磺胺嘧啶和甲氧苄啶的比例分别为9.57∶1~11.01∶1、6.30∶1~9.36∶1、5.40∶1~10.39∶1和4.20∶1~20.64∶1,均维持在1∶1~40∶1的理想抑菌配比范围内.研究结果表明温度对药物在罗非鱼体内的吸收及消除影响显著,可提高药物的最大血药质量浓度与消除速率,但对复方磺胺嘧啶在血浆中的比值影响不显著.

    Abstract:

    【Objective】To investigate the pharmacokinetics and changes of sulfadiazine and trimethoprim in the blood of Oreochromis niloticus at different water temperatures.【Method】Compound sulfadiazine which contained two composition of sulfadiazine and trimethoprim was orally administered to O. niloticus at a single dosage of 120 mg/kg at 18,23,28 and 33 ℃.The concentration of sulfadiazine and trimethoprim in O. niloticus plasma was determined by HPLC method.【Result and conclusion】Results showed that higher peak plasma concentration(Cmax) of sulfadiazine was 12.41,19.60, 22.48 and 30.78 μg/mL at 18, 23, 28 and 33 ℃,the Cmax of trimethoprim was 1.22, 2.06, 2.44 and 2.70 μg/mL respectively,and a higher peak plasma concentration was found at a higher temperature. The elimination(t1/2 ke) of sulfadiazine was 18.22, 17.89, 16.90 and 12.99 h at 18, 23, 28 and 33 ℃;t1/2 ke of trimethoprim was 16.39, 7.08, 5.99 and 4.04 h respectively. Fast elimination of trimethoprim and sulfadiazine was observed at a higher temperature in O. niloticus. Concentration ratios of sulfadiazine/trimethoprim were 9.57∶1-11.01∶1, 6.30∶1-9.36∶1,5.40∶1-10.39∶1 and 4.20∶1-20.64∶1 within 10 h after administration at the synergistic activity ratios ranging of 1∶1-40∶1. The results show that the temperature can significantly affect the absorption and elimination of the drugs in O. niloticus, improving the maximum plasma concentration. It also speeds up the elimination of the drugs, but has little effect on the ratio of compound sulfadiazine.

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肖贺,王伟利,姜兰,鞠晶,罗理,邓玉婷,谭爱萍.不同温度下复方磺胺嘧啶在罗非鱼体内的药代动力学[J].华南农业大学学报,2014,35(6):13-18

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  • 收稿日期:2014-02-21
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  • 在线发布日期: 2014-10-28