苯酰甲硝唑干混悬剂的人体生物等效性研究

Studies of the Bioequivalence of Benzoyl Metronidazole Dry Suspension

目的考察苯酰甲硝唑混悬剂的人体生物等效性。方法采用随机、开放、双周期交叉试验设计,将18例男性健康受试者随机平均分为两组,分别单剂量口服1 280 mg受试制剂苯酰甲硝唑混悬剂或参比制剂苯酰甲硝唑胶囊,经1周清洗期后交叉服药。采用高效液相色谱法测定给药后不同时间甲硝唑的血药浓度,比较两制剂的生物等效性。结果苯酰甲硝唑受试制剂与参比制剂的主要药动学参数Cm ax分别为(10.79±0.96)和(10.12±2.12)μg.mL-1,tm ax分别为(4.00±0.84)和(4.67±1.14)h,t1/2分别为(10.69±2.46)和(10.80±2.00)h,AUC0→t分别为(196.25±30.67)和(191.95±30.13)μg.h-1.mL-1。AUC0→∞分别为(207.26±37.46)和(202.64±34.49)μg.h-1.mL-1。受试制剂的相对生物利用度为(103.60±17.50)%。结论该试验所建立的方法灵敏、准确、简便,受试制剂与参比制剂生物等效。

Objective To study the bioequivalence of the 2 preparations of benzoyl metronidazole in the human body. Methods 18 healthy male subjects were divided into 2 equal groups with a randomized, open and double-blind crossover experimental design. Subjects of the 2 groups were given each a single oral dose of 1 280 mg of the test preparation benzoyl metronidazole suspension and reference preparation benzoyl metronidazole capsules, respectively. The serum concentrations of the drug were then determined with HPLC at different time points after the medication and the bioequivalence of the 2 preparations was compared. Results The main pharmacokinetic parameters of the test preparation benzoyl metronidazole suspension and reference preparation benzoyl metronidazole capsule were as follows： Camx were （10.79 ±0.96）μg ·mL^-1 and （10.12 ±2.12）μg·mL^-1,t max（4.00±0.84）hand（4.67±1. 14）h,t1/2, （10.69±2.46）h and（10.80±2.00）h; AUC（0→∞） （196.25 ± 30.67） μg ·h^-1·mL^-1 and （ 191.95 ± 30. 13 ） μg · h^-1· mL^-1 , AUC（0→∞） （ 207.26 ± 37.46 ）μg· h^-1·mL^-1 and （ 202.64 ± 34.49）μg ·h^-2· mL^-1 , respectively. The relative bioavailability of the test preparation benzoyl metronidazole suspension was （ 103.60 ± 17.50） %. Conclusion The method used in the study was shown to be sensitive, accurate and handy and the Results showed that the two preparations of benzoyl metronidazole were bioequivalent.