截短侧耳素衍生物BC-7013在鸡体内的药物动力学和生物利用度研究
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国家自然科学基金(31172359)


Research on pharmacokinetics and bioavailability of pleuromutilin derivative BC-7013 in chickens
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    【目的】研究截短侧耳素衍生物BC-7013 在鸡体内的药物动力学(简称药动学)特征及生物利用度.【方法】 6周龄健康白羽肉鸡20只随机分为2组,雌雄各半,分别进行单剂量静脉注射(简称静注,2.5 mg·kg-1)和单剂量口服(15 mg·kg-1)截短侧耳素衍生物BC-7013.以高效液相色谱-串联质谱(HPLC-MS/MS)内标法定量测定血浆中衍生物BC-7013的浓度,采用WinNonlin 5.2药动学软件的非房室模型统计矩原理分析药物浓度时间数据,并计算其药动学参数.【结果和结论】 鸡静注给药后药动学参数为:t1/2β =(1.37±0.14) h,Vd=(1.87±0.25) L·kg-1,AUC(0→∞) =(2.83±0.56) μg·mL-1·h,CL=(1.14±0.28) L·h-1·kg-1;鸡口服给药后药动学参数为:tmax =(1.94±0.26) h,Cmax =(126.18±6.54) ng·mL-1,AUC(0→∞) =(1.38±0.21) μg·mL-1·h,MRT=(9.49±0.57) h,F =(10.37±1.48)%.截短侧耳素衍生物BC-7013在鸡体内的药动学特征表现为:静注给药后分布广,消除快;口服给药后吸收较快但不完全,生物利用度较低.

    Abstract:

    【Objective】The pharmacokinetical characteristics and bioavailability of pleuromutilin derivative BC-7013 in chickens were investigated. 【Method】 Twenty chickens were randomly divided into two groups for pharmacokinelical experiments after a single intravenous (2.5 mg·kg-1) and oral administration (15 mg·kg-1). Blood samples were collected at different intervals after the administration of derivative BC-7013. The concentrations of derivative BC-7013 in plasma were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with internal standard method. Plasma concentration-time profiles of derivative BC-7013 were analyzed by using non-compartmental analysis WinNonlin 5.2 software. 【Result and conclusion】 The main pharmacokinetical parameters of i.v. administration were as follows:t1/2β =(1.37±0.14) h,Vd=(1.87±0.25) L·kg-1,AUC(0→∞) =(2.83±0.56) μg·mL-1·h,CL=(1.14±0.28) L·h-1·kg-1. The major pharmacokinetical parameters of oral administration were as follows:tmax =(1.94±0.26) h,Cmax =(126.18±6.54) ng·mL-1,AUC(0→∞) =(1.38±0.21) μg·mL-1·h,MRT=(9.49±0.57) h,F =(10.37±1.48)%. The results show that the pharmacokinetical characteristics of pleuromutilin derivative BC-7013 in healthy chicken manifest wide distribution, rapid elimination as well as incomplete absorption and low oral bioavailability.

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杨德学,陈良柱,赖丽虹,任妙贤,张桂君,潘志坤,方炳虎.截短侧耳素衍生物BC-7013在鸡体内的药物动力学和生物利用度研究[J].华南农业大学学报,2015,36(4):26-31

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  • 收稿日期:2014-04-21
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  • 在线发布日期: 2015-07-10