Study On Bioequivalence Of Cefprozil Capsules In Chinese Healthy Volunteers

Objective:The study aimed to determine the cis and trans isomer of cefprozil of the test provided by QILU Pharmacecutical Company,to enter the systemic circulation in the same extent and rate in healthy voluntees,using a single does,two-way cross over study design with a wash-out period of 7 days,and to evaluate the bioequivalence of cefprozil test and reference.Methods:A randomized, two-way cross over,two-perrod trial design was used in the study.20 health male subjects were randomly divided into 2 treatment groups.One group received 500mg test preparation, and another group received 500mg reference preparation.4ml of blood were collected before and 0.25,0.5,0.75,1,1.5,2,3,4,5,6, 80.75,1,1.5,2,3,4,5,6,8,10,12h after dosing. The blood samples were collected and centrifuged in hepaeinized tubes. The plasma samples was separated, and kept at-20℃until assayed.Repeat above steps next week.The plasma concentration of the cis and trans isomer of cefprozil were determined by HPLC method.The statistical analysis of the cis and trans isomer of cefprozil pharmacokinetic parameters was carried out by DAS 2.0. The relative bioavailability of the test preparation was evaluated by the AUC0-t value. The main pharmacokinetic parameters were analysized by variance analysis, two one-sided test and (1-2a) confidence intervals to valuate the bioequivalence of cefprozil test and reference preparations.Results: The mainr pharmacokinetic parameters of the cis- isomer of cefprozil of test and reference preparation were shown as follows:t1/2 were (1.390±0.384) h and (1.423±0.442)h, respectively. Tmax were (1.825±0.520)h and (1.650±0.401)h, respectively. Cmax were (7.199±1.237)μg·ml-1and (6.693±1.064)μg·ml-1, respectively. AUC0-twere(22.069±4.535)μg·ml-1·h and (20.329±3.038)μg·ml-1·h,respectively. AUC0-∞,were (22.186±4.566)μg·ml-1·h and (20.441±3.042)μg·ml-1·h, respectively.The main pharmacokinetic parameters of trans-cefprozil isoform of test and reference preparation as follows:t1/2 were (1.115±0.383) h and (1.015±0.247)h, respectively.Tmax were (1.750±0.303)h and (1.563±0.396)h,respectively.Cmax were (0.744±0.243)μg·ml-1 and (0.676±0.171)μg·ml-1,respectively.AUC0-t were (1.837±0.376)μg·ml-1·h and (1.730±0.398)μg·ml-1·h,respectively.AUC0-∞were (1.959±0.449)μg·ml-1·h and (1.805±0.408)μg·ml-1·h, respectively。 The relative bioavailability of the cis and trans isomers of cefprozil capsule for test preparation were 108.3%±11.7% and 107.7%±15.0%, respectively.Conclusion:①The relative bioavailability of the cis- and trans- isomers of cefprozil capsule for test preparation were 108.3%±11.7% and 107.7%±15.0%,respectively.②The AUC0-∞and AUC0-t of cis- and trans- cefprozil have no significant differences between period,but have significant differences between preparations after single oral dose of cefprozil capsule for test and reference preparation according to the multi- factor analysis. The Cmax of cis- cefprozil have significant difference between drugs and period.③The statistical analysis of pharmacokinetic parameters showed that the preparations of test and reference were bioequivalentil.④During the test, there was no obvious adverse reaction for volunteers after taking the test and reference preparation. The medical results were no significant differences before and after study.