两种单硝酸异山梨酯缓释片在中国健康人体内的生物等效性研究

目的：研究2种单硝酸异山梨酯缓释片在中国健康人体内的药物动力学特征和生物等效性。方法：采用单次给药、随机、开放、两周期、双交叉的试验设计，健康受试者分别在空腹和餐后条件下口服单硝酸异山梨酯缓释片受试制剂与参比制剂各40 mg，利用高效液相色谱-质谱法测定血浆中药物浓度，计算相关药动学参数并评价其生物等效性。结果：（1）空腹试验中受试制剂与参比制剂的C_max分别为（546.52±102.32），（521.71±85.80）ng·mL^-1，AUC_0-t分别为（7 398.89±1 298.56），（7 278.29±1 173.38）ng·h·mL^-1，AUC_0-∞分别为（7 488.82±1 311.38），（7 372.49±1 172.09）ng·h·mL^-1。（2）餐后试验中受试制剂与参比制剂的C_max分别为（529.41±82.52），（502.21±65.15）ng·mL^-1，AUC_0-t分别为（7 305.10±1 320.74），（7 066.12±1 136.99）ng·h·mL^-1，AUC_0-∞分别为（7 393.21±1 317.32），（7 160.22±1 140.11）ng·h·mL^-1。（3）空腹和餐后试验中受试制剂与参比制剂C_max、AUC_0-t和AUC_0-∞几何均数的90%CI均在80.00%~125.00%范围内，表明2种制剂具有生物等效性。结论：单硝酸异山梨酯缓释片受试制剂与参比制剂在中国健康志愿者中具有生物等效性。

Bioequivalence study of two isosorbide mononitrate sustained-release tablets in Chinese healthy volunteers

OBJECTIVE To investigate the bioequivalence and pharmacokinetic characteristics of two kinds of isosorbide mononitrate sustained-release tablets in Chinese healthy volunteers.METHODS A randomized, crossover, two periods, and one dose clinical trial was performed in this study. The healthy volunteers were given 40 mg isosorbide mononitrate sustained-release tablets of test (T) and reference (R) preparations respectively under fasting condition and fed condition. The plasma concentration of isosorbide mononitrate was determined by HPLC-MS/MS. Pharmacokinetic parameters of isosorbide mononitrate were calculated and the bioequivalence was evaluated.RESULTS In fasting test, the pharmacokinetic parameters of T and R preparations were as follows:C_max were (546.52±102.32) and (521.71±85.80) ng·mL^-1. AUC_0-t were (7 398.89±1 298.56) and (7 278.29±1 173.38) ng·h·mL^-1, AUC_0-∞ were (7 488.82±1 311.38) and (7 372.49±1 172.09)ng·h·mL^-1, respectively. In fed test, the pharmacokinetic parameters of T and R preparations were as follows:C_max were (529.41±82.52) and (502.21±65.15) ng·mL^-1, AUC_0-t were (7 305.10±1 320.74) and (7 066.12±1 136.99) ng·h·mL^-1, AUC_0-∞ were (7 393.21±1 317.32) and (7 160.22±1 140.11) ng·h·mL^-1, respectively. In fasting and fed tests, the 90% CI of the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ between T and R preparations were all within the range of 80.00%-125.00%, suggesting the two preparations were bioequivalent.CONCLUSION The two kinds of isosorbide mononitrate sustained-release tablets are bioequivalent in Chinese healthy volunteers.