左氧氟沙星片及胃漂浮缓释微丸在大鼠体内的药动学比较研究  

Comparative Study on Pharmacokinetics of Levofloxacin Tablets and Levofloxacin Gastric Floating Sustained-release Pellets in Rats

作　　者：邱妍川[1] 钟玲[2] 何静[1] QIU Yanchuan;ZHONG Ling;HE Jing(Chongqing Medical and Pharmaceutical College,Chongqing 401331,China;Research and Development Center,Yao Pharma.Co.,Ltd.,Chongqing 401121,China)

机构地区：[1]重庆医药高等专科学校药学院,重庆401331 [2]重庆药友制药有限责任公司研发中心,重庆401121

出　　处：《中国药房》2019年第10期1347-1351,共5页China Pharmacy

基　　金：重庆市科学技术委员会社会民生科技创新专项项目(No.cstc2016shmszx130078);重庆市卫生计生委医学科研项目(No.2015MSXM098)

摘　　要：目的:建立测定大鼠血浆中左氧氟沙星浓度的方法,并比较左氧氟沙星片及胃漂浮缓释微丸在大鼠体内的药动学差异。方法:将SD大鼠随机分为左氧氟沙星片组和左氧氟沙星胃漂浮缓释微丸组,每组6只。分别空腹灌胃相应药物40 mg/kg(以生理盐水为溶剂),并于给药前及给药后0.25、0.5、1、2、4、8、12、24 h自眼眶取血0.3 mL,采用超高效液相色谱法(UPLC)测定大鼠血浆中左氧氟沙星的浓度。色谱柱为Waters Acquity UPLC BEH C_(18),流动相为0.1%甲酸溶液-乙腈(78∶22,V/V),流速为0.3 mL/min,检测波长为294 nm,柱温为40℃,进样量为2μL。采用DAS 3.0软件计算两组大鼠的药动学参数,采用F检验考察两者的差异。结果:左氧氟沙星检测质量浓度的线性范围为0.20～20.12μg/mL,定量下限为0.20μg/mL,最低检测限为0.04μg/mL;日内、日间RSD均小于10%,回收率符合2015年版《中国药典》生物样品定量分析的相关要求。大鼠单剂量灌胃左氟氧沙星片及胃漂浮缓释微丸后的平均药-时曲线均符合二室模型,达峰浓度(c_(max))分别为(12.13±1.67)、(8.76±1.13)μg/mL,达峰时间(t_(max))分别为(0.86±0.15)、(2.48±0.45)h,消除半衰期(t_(1/2β))分别为(4.67±0.95)、(6.67±1.01)h,药-时曲线下面积(AUC_(0-t))分别为(42.95±4.21)、(126.48±9.44)μg·h/mL,AUC_(0-∞)分别为(50.66±6.72)、(132.61±10.63)μg·h/mL。与左氧氟沙星片比较,左氧氟沙星胃漂浮缓释微丸的c_(max)显著降低,t_(max)、t_(1/2β)、AUC、平均驻留时间均显著延长或升高(P<0.05);相对生物利用度为294%。结论:本研究建立的UPLC法操作简便,专属性强,灵敏度、精密度高,可用于大鼠血浆中左氧氟沙星质量浓度的检测及药动学的研究。将左氧氟沙星制成胃漂浮缓释微丸后,其药动学参数变化明显,药物在大鼠体内的滞留时间明显延长,生物利用度显著提高。OBJECTIVE:To establish a method for the concentration determination of levofloxacin in rat plasma and compare the pharmacokinetic difference between Levofloxacin tablets and gastric floating sustained-release pellets in rats.METHODS:SD rats were randomly divided into Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group,with 6 rats in each group.They were given relevant medicine intragastrically 40 mg/kg(taking normal saline as solvent),and the blood samples 0.3 mL were collected before medication and 0.25,0.5,1,2,4,8,12,24 h after medication.The plasma concentration of levofloxacin in rats was determined by UPLC.The determination was performed on Waters Acquity UPLC BEH C18 column with mobile phase consisted of 0.1% formic acid-acetonitrile(78∶22,V/V)at the flow rate of 0.3 mL/min.The detection wavelength was set at 294 nm,and column temperature was 40℃.The sample size was 2μL.The pharmacokinetic parameters of rats were calculated by using DAS 3.0 software,and the difference between them were detected by F-test.RESULTS:The linear range of levofloxacin was 0.20-20.12μg/mL,and limit of quantitation was 0.20μg/mL.The limit of detection was 0.04μg/mL.The intra-day and inter-day RSDs were less than 10% .The recoveries were all in line with the related requirements of quantitation analysis of the biological samples stated in 2015 edition of Chinese Pharmacopeia.Average drug concentration-time curves of single dose of Levofloxacin tablets group and Levofloxacin gastric floating sustained-release pellets group were all in line with two-compartment model after intragastric administration.The pharmacokinetic parameters cmax were(12.13±1.67)and(8.76±1.13)μg/mL;tmax were(0.86±0.15)and(2.48±0.45)h;t1/2βwere(4.67±0.95)and(6.67±1.01)h;AUC0-t were(42.95±4.21)and(126.48±9.44)μg·h/mL;AUC0-∞were(50.66±6.72)and(132.61±10.63)μg·h/mL,respectively.Compared with Levofloxacin tablets,cmax of Levofloxacin gastric floating sustained-release pellets were decreased significant

关 键 词：左氧氟沙星 胃漂浮缓释微丸 超高效液相色谱法 血药浓度 药动学 大鼠 

分 类 号：R945[医药卫生—微生物与生化药学] R969.1[医药卫生—药剂学]