Bioequivalence of selegiline hydrochloride tablets in healthy Chinese subjects
OBJECTIVE To study the bioequivalence of generic and original selegiline hydrochloride tablets in Chinese healthy subjects respectively under fasting and fed conditions.METHODS A total of 84 healthy subjects were enrolled in this study,including 36 cases of fasting administration and 48 cases of fed administration.The fasting administration trial was a ran-domized,open,two-sequence,four-cycle,completely repeated crossover design.The subjects were randomly divided into 2 groups,18 cases in each group.The fed administration trial was a randomized,open,three-sequence,three-cycle,partially repeated crossover design.The subjects were randomly divided into 3 groups,16 cases in each group.Single oral dose of 5 mg test and reference selegiline hydrochloride tablets was taken in each cycle,and the washout period was 14 days.The blood samples were obtained at the planned time points.Plasma concentrations of selegiline and desmethyl selegiline were determined by a validated LC-MS/MS method.Phoenix WinNonlin 8.1 software was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two preparations.RESULTS The major pharmacokinetic parameters of the test and reference selegiline under fasting condition were as follows:Cmax(2 265±1 849)and(2 810±2 658)pg·mL-1,AUC0-t(1 886±1 831)and(1 996±2 102)pg·mL-1·h,AUC0-∞(1 938±1 860)and(2 051±2 133)pg·mL-1·h.The major pharmacokinetic parameters of the test and reference selegiline under fed condition were as follows:Cmax(3 042±2 211)and(3 110±2 566)pg·mL-1,AUC0-t(4 081±3 363)and(4 025±3 215)pg·mL-1·h,AUC0-∞(4 175±3 448)and(4 129±3 307)pg·mL-1·h.In the fasting and fed tests,the 90％CI of the geometric mean ratios of the main pharmacokinetic parameters between the test and reference prepara-tions were all within the range of 80％-125％,which met the criteria for bioequivalence evaluation.A total of 79 adverse events(28 under fasting condition and 51 under fed condition)occurred during the trial period,and no serious adverse event occurred.CONCLUSION In fasting and postprandial state,the test and reference preparations are bioequivalent and safe in healthy subjects..
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