低氧与常氧状态下罗红霉素在大鼠体内的药代动力学比较  

Pharmacokinetic comparison of roxithromycin under normoxic and hypoxic conditions in rats by UPLC/MS /MS

作　　者：邵涛[1,2] 秦一[1] 徐平湘[1,3] 徐唯哲[1] 赵亮[1] 马毅[1] 郝维佳[1] 薛明[1,3] 

机构地区：[1]首都医科大学基础医学院药理学系,北京100069 [2]中国航天科工集团七三一医院药剂科,北京100074 [3]生物医学检测技术与仪器北京实验室,北京100069

出　　处：《中国药理学通报》2016年第11期1596-1601,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81173121;81573683)

摘　　要：目的研究比较在低氧和常氧条件下,常用抗生素罗红霉素在大鼠体内的药代动力学特征。方法建立快速高效的超高效液相质谱联用法,测定大鼠血浆中罗红霉素的浓度。SD大鼠灌胃给予罗红霉素(10 mg·kg^(-1)),测定不同时间点的大鼠血浆药物浓度,分别计算低氧与常氧大鼠的主要药代动力学参数,并进行统计分析。结果在1~1 000μg·L^(-1)浓度间,罗红霉素在血浆中有良好的线性关系,定量下限为1μg·L^(-1)。罗红霉素在常氧和低氧大鼠体内主要药动学参数分别为:AUC_(0-t)7 576μg·h·L^(-1)和3 761μg·h·L^(-1);MRT_(0-t)5.6 h和7.7 h;T_(1/2)3.4 h和3.9 h;t_(max)3.1h和3.4 h;C_(max)1 116μg·L^(-1)和372μg·L^(-1);CL 1.5和3.0 L·h^(-1)·kg^(-2)。与常氧大鼠药动学参数比较,低氧状态下罗红霉素在大鼠体内的药动学参数C_(max)和AUC均有明显降低。结论低氧条件下,罗红霉素在大鼠体内的体内暴露量明显降低,结果为罗红霉素在低氧状态下的给药方案优化和调整提供了重要的实验依据。Aim To study and compare the pharmaco-kinetic parameters of roxithromycin under normoxic andhypoxic rats. Methods A highly effective and rapid ultra-performance liquid chromatography with tandem mass spectrometry( UPLC-MS / MS) method with positive electrospray ionization source was successfully developed and validated for quantification of roxithromycin in rat plasma. Sprague-Dawley rats were randomly divided into the hypoxia and normoxic groups. Each rat obtained a single dose of roxithromycin with 10 mg ·kg^(-1)via intragastric administration. The pharmacokinetic parameter comparison between normoxic and hypoxic groups was calculated by SPSS software using independent sample t test method. Results The main pharmacokinetic parameters of roxithromycin between the normoxic and hypoxic rats were: the AUC_( 0-t)7 576and 3 761 μg·h·L^(-1),MRT_( 0-t)5. 6 and 7. 7 h,T_(1 /2)3. 4 h and 3. 9 h,CL 1. 5 and 3. 0 L · h^(-1)·kg^(-2),t_(max)3. 1 and 3. 4 h,C_(max)1 116 and 372 μg·L^(-1),respectively. The levels of Cmaxand AUC of roxithromycin in hypoxic rats were statistically lower than those in normoxic rats. Conclusion The exposure level of roxithromycin in hypoxic rats markedly decreased. Our results may provide an important experimental basis to adjust the dosage for roxithromycin in hypoxic clinical practice.

关 键 词：罗红霉素 超高效液相色谱-质谱联用法 低氧 常氧 药代动力学 大鼠血浆 

分 类 号：R-332[医药卫生] R845.22