关键词: 阿司匹林, 乙酰水杨酸, 生物等效性, 安全性评价

Abstract:

Objective To evaluate the bioequivalence and safety of aspirin enteric-coated tablets in healthy Chinese adult. Methods A single-center, randomized, open, two-preparation, two-sequence, four-cycle, fully replicated design was used. The subjects took orally one tablet of test (T) or reference (R) preparation on fasting or fed condition every cycle. The plasma concentration of acetylsalicylic acid (ASA) was determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS) method at different time points, and the bioequivalence and safety of the two formulations were evaluated. Results In the main results for pharmacokinetic parameters of T and R under fed condition, C_max were (690.97±196.91) and (669.28±337.40) ng·ml^-1, AUC_0-t were (867.37±228.64) and (821.16±349.85) ng·h·ml^-1, AUC_0-∞ were (883.48±233.72) and (923.59±287.95) ng·h·ml^-1, T_max were (8.98±2.47) and (10.69±3.75) h. In the main result for pharmacokinetic parameters of T and R under fasting condition, C_max were (466.83±222.89) and (441.42±211.99) ng·ml^-1, AUC_0-t were (753.24±269.49) and (678.50±278.85) ng·h·ml^-1, AUC_0-∞ were (809.11±309.27) and (726.51±267.00) ng·h·ml^-1, T_max were (5.81±2.53) and (6.41±2.47) h. The geometric mean ratios of the main pharmacokinetic parameters C_max, AUC_0-t and AUC_0-∞ in the fed group were within the range of 80.00% to 125.00%, therefore the two formulations were bioequivalent. However,the fasting group did not meet the relevant criteria, and the two preparations were not equivalent. During the study period, 0 case and 2 cases of adverse events occurred under the fasting and the fed condition. No serious adverse events occurred. Conclusion The two kinds of aspirin enteric-coated tablets were bioequivalent in human under the fed condition, but not in the human under fasting conditions, and the formulations were safe and well tolerated.

Key words: aspirin, acetylsalicylic acid, bioequivalence, safety evaluation