丁苯酞注射液在中国健康人体内的生物等效性研究

目的：研究空腹条件下静脉滴注受试制剂丁苯酞注射液（规格：5 mL：25 mg，南京优科制药有限公司生产）与参比制剂丁苯酞氯化钠注射液（商品名：恩必普）在健康受试者体内的生物等效性及安全性。方法：采用随机、开放、两周期、双交叉给药试验设计，选择24名健康受试者分别交叉单次静脉注射丁苯酞注射液受试制剂和参比制剂100 mL，输液量（100±5） mL（输液泵允许有5%以内的误差），时间55 min。采用液相色谱-串联质谱（LC-MS /MS）法测定血浆中丁苯酞浓度，使用WinNonlin 6.4软件计算主要药动学参数，并进行生物等效性评价。结果：24名健康受试者输注受试制剂和参比制剂后，丁苯酞的主要药动学参数：AUC0-t：（541.0±78.6）ng·mL-1·h和（525.0±76.1）ng·mL-1·h；AUC0-∞：（571.0±82.1） ng·mL-1·h和（555.0±88.1） ng·mL-1·h；Cmax：（295.0±62.7） ng/mL和（291.0±56.5） ng/mL；Tmax分别为0.92（0.33, 0.92）h和0.92（0.33, 0.93）h。t1/2分别为（16.60±6.85） h和（15.80±5.88）h。受试制剂和参比制剂的AUC0-t，AUC0-∞，Cmax的几何均数比值（GMR）的90%置信区间均在80.0%～125.0%的范围内。结论：受试制剂丁苯酞注射液与原研丁苯酞注射液具有生物等效性。

Bioequivalence study of buthlphthalide injection in Chinese healthy volunteers

AIM: To establish a method to investigate pharmacokinetics and bioequivalence of buthlphthalide injection. METHODS: An open, randomized, and two-cycle crossover study was conducted in 24 healthy volunteers. Plasma concentrations of buthlphthalide were determined by LC-MS/MS after administering a single dose of reference drug or test drug. Main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. RESULTS: For the test drug and the reference drug, the main pharmacokinetic parameters of flurbiprofen were as follows: AUC0-t was (541.0±78.6) ng·mL-1·h and (525.0±76.1) ng·mL-1·h, AUC0-∞ was (571.0±82.1) ng·mL-1·h and (555.0±88.1) ng·mL-1·h, Cmax was (295.0±62.7) ng/mL and (291.0±56.5) ng/mL, and the median of Tmax was 0.92 (0.33, 0.92) h and 0.92 (0.33, 0.93) h, respectively. Under two kinds of conditions, 90%CIs of AUC0-t, AUC0-∞ and Cmax of the test preparation were 80%-125% of the corresponding parameters of the reference preparation，and there was no statistical significance in Tmax between the two preparations (P＞0.05)．CONCLUSION: The test drug and the reference drug are bioequivalent．