氧氟沙星缓释片单次、多次给药人体药代动力学和生物等效性研究  

Single-dose and multi-dose pharmacokinetics and bioavailability of ofloxacin sustained-release tablets in healthy volunteers

作　　者：钟国平[1] 陈孝[2] 任斌[2] 钟诗龙[3] 邝翠仪[2] 黄丽慧[1] 曾桂雄[1] 王雪丁[1] 廖晓星[2] 黄民[1] 赵香兰[1] 

机构地区：[1]中山大学临床药理研究所 [2]中山大学附属第一医院 [3]广东省人民医院

出　　处：《中国临床药理学与治疗学》2013年第11期1260-1265,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的：研究氧氟沙星缓释片单次、多次给药的人体药代动力学特征，并与氧氟沙星片比较其缓释特征与生物等效性。方法：单次给药20例健康成年男性受试者随机分组，自身双周期交叉对照，单次口服药物400mg；多次给药18例健康成年男性受试者随机分组，自身双周期交叉对照，多次口服药物（参比制剂400mg／2次／d×5d，受试制剂400mg／次／d×5d）。通过反相HPLC法测定血浆氧氟沙星浓度，采用非房室模型计算药代动力学参数，并进行统计分析。结果：单次给药参比制剂与受试制剂的Cmax分别为（5382±1558）、（3419±1034）μg／L；Tmax分别为（1．7±0．6）、（4．2±1．8）h；t1／2分别为（8．2±1．0）、（7．6±1．8）h；MRT分别为（8．6±0．9）、（10．3±1．4）h；AUC分别为（33764±5297）、（31280±4412）／zg·L-1·h；AUC分另别为（34643±5356）、（32642±4257）Frel为（97．9±12．4）％。方差分析显示，MRT各参数受试制剂与参比制剂差异具有统计学意义；各参数受试制剂与参比制剂差异无统计学意义。等效性检验显示，受试制剂与参比制剂90％可信限。为89．0％～97．0％；AUC为91．4％～97．8％。多次给药参比制剂与受试制剂的Cmax分别为（3732±1502）、（3564±982）μg／L；Cmax分别为（750±193）、（438±89）分别为（1．5i0．5）、（3．7±1．7）h；AUCss分别为（32689±4786）、（33591±7929）分别为（1362±199）、（1405±337）μg／L；DF分别为（216．1±76．5）、（221．5i33．9）％；F刊为（102．9±22．5）％。方差分析显示，AUCss、DF受试制剂与参比制剂差异均无统计学意义。等效性检验显示，909／6可信限Cmax为80．8％～114．6％；AUCss为89．3％～111．9％；为89．5％～112．4％；DF为93。7％～122．4％。结论：受试制剂氧氟沙星缓释片相对于参比制剂氧氟沙星片，单次给药具有缓释动力�AIM. To study the singledose and multidose pharmacokinetics and bioavailability of ofloxacin sustainedrelease tablets in healthy volunteers. METHODS. The plasma concentra tions of ofloxacin were determined by a RP HPLC method. The reference or test prepara tion was given to healthy male volunteers ac cording to an open randomized crossover study. The pharmacokinetic parameters and bioavail ability of test preparation were compared with reference preparation. RESULTS：The main pharmacokinetic parameters of the test preparation and the reference preparation, the singledose were as follows： Cmax were （5382 ± 1558）and （3419±1034） μg/L, Tm were （1.7±0.6）and （4.2±1.8） h, tl/2 were（8.2±1.0） and（7.6±1.8） h, MRT were（8.6±0.9） and（10.3±1.4） hlAUC0t were （33764 ±5297） and（31280 ±4412） go L1 . h, AUC0 were （34643 ± 5356）and （32642±4257） μg. L. h. The rel ative bioavailability of reference to test prepara tion was （97.9 ±12.4）%. There were statistically significant difference about C T MRT between the reference preparation and test prep aration, but there were no statistically signifi cant difference about tl/2, AUC0t,UC0. The 90% confidence limit of AUC0t and AUC0 between the reference preparation and test preparation were 89.0% 97.0% and 91.4% 97.8% respectively. The multidose were as follows. Cm were （3732 ± 1502） and （3564±982） μg/L, Cmin were （750± 193）,（438 ±89） μg/L, Tmax were （1.5±0.5） and（3.7± 1.7） h, AUCss were （32689±4786） and（33591 ±7929） /μg . L-1 . h, Cv were（1362t199）and （1405±337）μg/L,DF were （216±76）and（222 ±34） . The relative bioavailability of reference to test preparation was （102.9±22.5）%. Therewere no statistically significant difference about C Ca,, AUCss, DF between the reference preparation and test preparation. The 90% con fidence limit of C AUCss, Car and DF were 80.8% 114.6%,89.3%111.9% ,89.5% 112.4% and 93.7% 122.4%. CONCLUSION. The results of statistics

关 键 词：氧氟沙星缓释片 高效液相色谱法 药代动力学 生物利用度 生物等效性 

分 类 号：R969[医药卫生—药理学]