头孢丙烯片的人体药动学和生物等效性

Study on pharmacokinetics and bioequivalence of cefprozil tablets in healthy volunteers

目的:建立HPLC法测定人血浆中头孢丙烯,研究国产头孢丙烯片(受试制剂A)在健康人体内的药动学特点,并评价其与参比制剂R的生物等效性。方法:20名男性健康受试者随机分为2组,进行单剂量双周期双交叉试验,分别口服500mg头孢丙烯受试制剂和参比制剂,2次试验间隔时间为7d。用HPLC法测定血浆中头孢丙烯浓度,计算其药动学参数。结果:受试制剂和参比制剂的主要药动学参数Cmax分别为(8.7±1.3)和(8.4±1.2)μg.mL-1;tmax分别为(1.9±0.5)和(1.7±0.5)h;t1/2分别为(1.30±0.16)和(1.31±0.12)h;CL/F分别为(16.2±2.8)和(14.1±2.4)L.h-1;MRT0-10分别为(2.83±0.28)和(2.8±0.3)h;MRT0-∞分别为(3.0±0.3)和(3.0±0.4)h;AUC0-10分别为(30.3±5.1)和(28.4±4.6)μg.h.mL-1;AUC0-∞分别为(31.0±5.2)和(29.2±4.6)μg.h.mL-1;由AUC0-10、AUC0-∞估算的受试制剂的相对生物利用度分别为(106.5±7.8)%和(106.2±7.2)%。结论:本实验方法准确、灵敏、特异性强、操作简便,适于头孢丙烯片的药动学和生物等效性研究,试验结果表明两制剂具有生物等效性。

OBJECTIVE To determine the content of cefprozil in human plasma by HPLC method in order to evaluate the pharmacokinetics and bioequivalence of cefprozil tablets （testing product and reference product） in healthy volunteers. METHODS 20 healthy male volunteers were divided randomly into two groups for single dose and two crossing test, each group was given with PO 500 mg testing product or reference product respectively. Wash out period is 7 days between two tests. The blood drug concentration was analyzed by HPLC and the pharmacokinetic parameters were calculated. RESULTS The main pharmacokinetic parameters of testing product and reference product were as follows： Cmax were（8. 7 ± 1.3）and （8. 4 ±1.2）μg·mL^- 1 ; tmax were（ 1.9 ±0. 5） and （ 1.7 ＋ 0. 5 ） h; t1/2 were （ 1.30 ＋ 0. 16 ） and （ 1. 31 ± 0. 12 ） h; CL/F were （ 16. 2 ±2. 8 ） and （ 14. 1 ± 2. 4）L·h^-1 ; MRT0-10 were（2. 83± 0. 28）and（2. 8 -＋ 0. 3）h; MRT0-∞ were（3. 0 ± 0. 3）and（3.0±0. 4）h; AUG0-10 were（30. 3 ± 5.1 ） and（28. 4 ＋ 4. 6）μg·h·mL^-1 ;AUC0-∞ were（31.0 ± 5.2）and（29. 2 ± 4. 6）μg·h·mL^-1. The relative bioavailability of AUG0-10 and AUC0-∞ were （106. 5 ±7. 8）% and （106. 2 ±7. 2）%. CONCLUSION The method was proved to be accurate,sensitive,specific and simple,which was suitable for the study of pharmacokinetics and bioequivalence of cefprozil tablets in healthy vohmteers. The testing product and reference product are bioequivalent.