急进高原对普萘洛尔药代动力学参数的影响  

Effect of acute exposure to high altitude on the pharmacokinetics of propranolol

作　　者：李文斌[1] 贾正平[1] 谢华[1] 张娟红[1] 王延玲[1] 郝颖[1] 王荣[1] 

机构地区：[1]兰州军区兰州总医院全军高原环境损伤防治重点实验室,兰州730050

出　　处：《中南大学学报（医学版）》2013年第9期909-914,共6页Journal of Central South University ：Medical Science

基　　金：国家科技部重大资助项目(2008ZXJ09014-010)~~

摘　　要：目的:研究急进高原环境对普萘洛尔药代动力学参数的影响。方法:健康清洁级雄性Wistar大鼠14只,体质量(200±20)g,按0.05 g/kg单次灌胃给予普萘洛尔制剂,于0,20,40 min和1,1.5,2,3,4,6,8,12,24 h在平原眼眶后静脉丛采血0.5 mL;经过7 d清洗期后,急进海拔4010 m高原,再次给药并采血,采用液相质谱串联质谱(liquid chromatography mass spectrometry and tandem mass spectrometry,LC-MS/MS)测定血浆中普萘洛尔的血药浓度,药物与统计(drug and statistics,DAS)2.0软件计算药物动力学参数,并进行二者药代动力学参数的比较。结果:急进高原组与平原组相比药时曲线下面积(areaunderconcentration-timecurve,AUC)增大442.61%,平均驻留时间(mean retention time,MRT)延长47.45%,半衰期(half-life,t1/2)延长73.13%,峰浓度(peak plasma concentration,Cmax)增高352.97%,总清除率(clearance,CL)下降80.87%,表观分布容积(apparent volume of distribution,V)降低68.94%。这些方面的差异二者之间均有统计学意义(P<0.05)。结论:在高原条件下,普萘洛尔的药代动力学参数发生显著变化,研究结果将为高原条件下普萘洛尔的合理用药提供参考依据。Objective：To study the pharmacokinetics of propranolol in Wistar rats after acute exposure to high altitude. Methods：Fourteen male Wistar rats （200±20） g were selected. After administration of propranolol tablets （0.05 g/kg, i.g.）, blood samples （3 mL） were collected at 0, 20, 40 min,1, 1.5, 2, 4, 6, 8, 12 and 24 h, respectively. The pharmacokinetic parameters were determined by LC-MS/MS and DAS 2.0 software. Results：The main pharmacokinetic area under concentration-time curve （AUC）, mean retention time （MRT）, half-life （t1/2） and peak plasma concentration （Cmax） of propranolol were increased by 442.61%, 47.45%, 73.13%and 352.97%, respectively, whereas Tmax and clearance （CL） were decreased by 80.87%and 68.94%, respectively. Conclusion：This study displays significant changes in the pharmacokinetics of propranolol under high altitude, which may provide evidence for clinical rational application of propranolol at high altitude.

关 键 词：普萘洛尔 药代动力学 急进高原 

分 类 号：R965[医药卫生—药理学]