瑞舒伐他汀钙片在中国健康受试者的生物等效性研究

目的：研究空腹及餐后状态下口服两种不同厂家生产的瑞舒伐他汀钙片在中国健康受试者体内的生物等效性。方法：本研究采用单中心、随机、均衡、开放、两序列、两周期、双交叉、单次给药的试验设计，空腹组和餐后组各入组52名健康受试者，每周期单次空腹/餐后口服瑞舒伐他汀钙片受试制剂或参比制剂10 mg，采用经过验证的LC-MS/MS法测定血浆中瑞舒伐他汀钙片的药物浓度，计算药动学参数，进行两种瑞舒伐他汀钙片的人体生物等效性及安全性评价。结果：空腹组受试制剂和参比制剂的t1/2分别为（10.1±3.9）h和（11.4±7.6）h，tmax分别为（3.9±1.1）h和（3.9±1.1）h，Cmax分别为（8.4±3.8）ng/mL和（8.3±4.2）ng/mL，AUC0-72分别为（75.8±34.7）ng·mL-1·h和（73.2±33.2）ng·mL-1·h，AUC0-∞分别为（77.4±34.9）ng·mL-1·h和（75.2±33.2）ng·mL-1·h。纳入生物等效性集（BES）的51例受试者的主要药动学参数Cmax、AUC0-72、AUC0-∞的几何均数比值（受试制剂/参比制剂）的90%置信区间统计结果均在可接受的等效范围内，分别为95.47%～109.71%、98.68%～110.57%、98.31%～109.50%。餐后给药组受试制剂和参比制剂的t1/2分别为（16.7±12.8）h和（14.5±5.5）h，tmax分别为（3.8±1.5）h和（3.7±1.4）h，Cmax分别为（5.9±2.9）ng/mL和（5.6±2.7）ng/mL，AUC0-72分别为（64.0±33.4）ng·mL-1·h和（62.2±32.0）ng·mL-1·h，AUC0-∞分别为（67.9±33.5）ng·mL-1·h和（65.5±31.9）ng·mL-1·h；Cmax、AUC0-72、AUC0-∞的几何均数比值（受试制剂/参比制剂）的90%置信区间统计结果分别为98.91%～110.68%、99.70%～108.03%、99.83%～108.32%。结论：瑞舒伐他汀钙片受试制剂和参比制剂在空腹和餐后状态下生物等效。服用高脂餐对瑞舒伐他汀钙片的药动学特征并无影响，瑞舒伐他汀钙片与食物或不与食物同服均可。

Bioequivalence of rosuvastatin calcium tablets in Chinese healthy subjects

AIM: To study the bioequivalence of rosuvastatin calcium tablets produced by two different manufacturers on a fasting and postprandial basis in Chinese healthy subjects. METHODS: A single-center, randomized, balanced, open, two-sequence, two-cycle, double-crossover, and single-dose trial design was used in this study. Each of the fasting group and the postprandial group was enrolled in 52 healthy subjects. Fasting/postprandial oral rosuvastatin calcium tablets 10 mg test preparation or reference preparation, the validated LC-MS/MS method was used to determine the concentration of rosuvastatin calcium tablets in plasma, and the pharmacokinetic parameters were calculated. Human bioequivalence and safety evaluation of two rosuvastatin calcium tablets were evaluated. RESULTS: The t1/2 of the test preparation and the reference preparation in the fasting group were (10.1±3.9) h and (11.4±7.6) h, the tmax was (3.9±1.1) h and (3.9±1.1) h, and the Cmax was (8.4±3.8) ng/mL and (8.3±4.2) ng/mL, AUC0-72 were (75.8±34.7) ng·mL-1·h and (73.2±33.2) ng·mL-1·h, AUC0-∞ were (77.4±34.9) ng·mL-1·h and (75.2±33.2) ng·mL-1·h; the geometric mean ratio of the major pharmacokinetic parameters Cmax, AUC0-72, AUC0-∞ of the 51 subjects included in the BES (test preparation/reference preparation) 90% confidence interval statistical results were acceptable. Within the equivalent range, they were 95.47%-109.71%, 98.68%-110.57%, and 98.31%-109.50%, respectively. The t1/2 of the test preparation and the reference preparation in the postprandial administration group were (16.7±12.8) h and (14.5±5.5) h, the tmax was (3.8±1.5) h and (3.7±1.4) h, and the Cmax was (5.9±2.9) ng/mL and (5.6±2.7) ng/mL, AUC0-72 were (64.0±33.4) ng·mL-1·h and (62.2±32.0) ng·mL-1·h, AUC0-∞ were (67.9±33.5) ng·mL-1·h and (65.5±31.9) ng·mL-1·h. The statistical results of the 90% confidence intervals of the geometric mean ratios (test preparations/reference preparations) of Cmax, AUC0-72, AUC0-∞ were 98.91%-110.68%, 99.70%-108.03%, and 99.83%-108.32%. CONCLUSION: Rosuvastatin calcium test preparation and reference preparation are bioequivalent in fasting and postprandial state. Taking a high-fat meal has no effect on the pharmacokinetic characteristics of Rosuvastatin calcium tablets. Rosuvastatin calcium tablets can be taken with or without food.