注射用头孢他啶在健康人体的生物等效性

Bioavailability and bioequivalence of ceftazidime for injection in healthy volunteers

目的:建立头孢他啶血浆浓度的测定方法,并评价注射用头孢他啶试验与参比制剂是否生物等效。方法:20名健康男性志愿者随机分为2组,采用开放、随机、双周期、自身对照交叉试验设计,对受试者进行单次肌内注射给药,两周期间的洗脱期为3d;采用高效液相色谱法测定头孢他啶经时血药浓度,利用DAS Ver2.0程序计算药动学参数并进行统计分析。结果:头孢他啶参比制剂(含头孢他啶1.0g)和试验制剂(含头孢他啶1.0g)的主要药动学参数Cmax分别为(27.5±5.5)mg.L-1和(27.6±5.4)mg.L-1,tmax分别为(1.2±0.5)h和(1.2±0.5)h,t1/2分别为(2.3±0.4)h和(2.15±0.26)h,AUC0-10分别为(115.3±16.8)mg.L-1.h和(108.2±19.5)mg.L-1.h,AUC0-∞分别为(122.4±16.7)mg.L-1.h和(113.7±20.2)mg.L-1.h。2组间Cmax、AUC0-10、AUC0-∞、tmax的差异均无显著性(P>0.05);试验制剂的Cmax、AUC0-10和AUC0-∞的90%可信区间均未超出参比制剂的80%～125%范围。试验制剂对参比制剂的相对生物利用度F为(93.9±11.2)%,RSD为11.9%。结论:头孢他啶血药浓度测定的方法适用;试验制剂与参比制剂具有生物等效性。

OBJECTIVE To establish a method for determining the plasma concentration of ceftazidime, and evaluate the bioavailability and bioequivalence of ceftazidime for injection of test and reference samples. METHODS Twenty healthy male volunteers were divided into 2 groups randomly, and an open label, randomized, self cross over study was performed, with single intramuscular injection of 1.0 g ceftazidime, and the washout interval was three days. The plasma ceftazidime concentration was determined by HPLC and the data were processed by DAS Ver 2. 0 program to obtain the pharmacokinetic parameters and to progress statistical analysis. RESULTS The main pharmacokinetic parameters： Cmax, tmax, t1/ 2, AUC0-10, AUC0-∞ of ceftazidime for injection of reference samples and test after single dose intramuscular injection and （1.0 g） were （27. 5 ± 5.5）mg·L^-1 and （27. 6 ±5.4）mg·L^-1 ; （1.2 ±0. 5）h and （1.2 ±0. 5）h; （2. 3 ±0.4）h and （2. 15 ±0.26）h; （115.±16. 8）mg·L^-1·h and （ 108.2 ±19.5 ） mg·L^-1·h; （ 122.4 ±16. 7）mg·L^-1·h and （ 113.7 ±20.2）mg·L^-1·h. There was no significant difference in Cmax, tmax, AUC0-10, AUC0-∞ between the two groups （P〉0. （15）. and Cmax, AUC0-10, AUC0-∞ of test preparation（90% confidence interval）were in the range of 80%- 125 % of reference preparation. Relative bioavailability F of ceftazidime for injection of test sample was （93.9 ± 11. 2） %, and RSD was 11.9%. CONCLUSION The method established is suitable for determining the plasma ceftazidime concentration, and the two preparations are bioequivalent.