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

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 400 mg;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 400 mg/2次/d×5 d,受试制剂 400 mg/次/d×5 d)。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C_max分别为(5382±1558)、(3419±1034)μg/L;T_max分别为(1.7±0.6)、(4.2±1.8) h;t_1/2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_0-t分别为(33764±5297)、(31280±4412) μg·L^-1·h;AUC_0→∞分别为(34643±5356)、(32642±4257)μg·L^-1·h;F_rel为(97.9±12.4)%。方差分析显示,C_max、T_max、MRT各参数受试制剂与参比制剂差异具有统计学意义;t_1/2、AUC_0-t、AUC_0→∞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AUC_0-t为 89.0%~97.0%;AUC_0→∞为 91.4%~97.8%。多次给药参比制剂与受试制剂的C_max分别为(3732±1502)、(3564±982) μg/L;C_min分别为(750±193)、(438±89) μg/L;T_max分别为(1.5±0.5)、(3.7±1.7) h;AUC_SS分别为(32689±4786)、(33591±7929) μg·L^-1·h;C_av分别为(1362±199)、(1405±337) μg/L;DF分别为(216.1±76.5)、(221.5±33.9)%;F_rel为(102.9±22.5)%。方差分析显示,C_max、C_av、AUC_SS、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,90%可信限C_max为 80.8% ~114.6%;AUC_SS为 89.3%~111.9%;C_av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学特征及吸收程度生物等效,多次给药达稳态时具有生物等效性。

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

AIM: To study the single-dose and multi-dose pharmacokinetics and bioavailability of ofloxacin sustained-release tablets in healthy volunteers.METHODS: The plasma concentrations of ofloxacin were determined by a RP-HPLC method. The reference or test preparation was given to healthy male volunteers according to an open randomized crossover study.The pharmacokinetic parameters and bioavailability of test preparation were compared with reference preparation.RESULTS: The main pharmacokinetic parameters of the test preparation and the reference preparation, the single-dose were as follows: C_max were (5382± 1558)and (3419±1034) μg/L, T_max were (1.7±0.6)and(4.2±1.8) h, t_1/2 were(8.2±1.0) and(7.6±1.8) h, MRT were(8.6±0.9) and(10.3±1.4) h;AUC_0-t were (33764±5297) and(31280±4412) μg·L^-1·h,AUC_0→∞ were (34643±5356)and (32642±4257) μg·L^-1·h. The relative bioavailability of reference to test preparation was (97.9±12.4)%.There were statistically significant difference about C_max,T_max,MRT between the reference preparation and test preparation, but there were no statistically significant difference about t_1/2,AUC_0-t,AUC_0→∞. The 90% confidence limit of AUC_0-t and AUC_0→∞ between the reference preparation and test preparation were 89.0%-97.0% and 91.4%-97.8% respectively. The multi-dose were as follows: C_max were (3732±1502)and (3564±982) μg/L, C_min were (750±193),(438±89) μg/L,T_max were (1.5±0.5) and(3.7±1.7) h, AUC_SS were (32689±4786) and(33591±7929) μg·L^-1·h, C_av were(1362±199)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)%. There were no statistically significant difference about C_max,C_av,AUC_SS, DF between the reference preparation and test preparation. The 90% confidence limit of C_max, AUC_SS,C_av 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 analysis showed that the test preparation exhibited sustained-release characteristics, and it was bioequivalent between the test preparation and the reference preparation.