国产氟比洛芬酯注射液中国健康志愿者人体生物等效性研究

Study on the Bioequivalence of Domestic Flurbiprofen Axetil Injection in Chinese Healthy Volunteers

目的:评价国产氟比洛芬酯注射液的生物等效性与安全性。方法:采用随机、开放、两周期交叉给药试验,选择24名健康受试者分别交叉单次静脉注射氟比洛芬酯注射液受试制剂和参比制剂5 ml,输注时间(70±3)s。采用液相色谱-串联质谱(LC-MS/MS)法测定血浆中氟比洛芬浓度,使用PhoenixWinNonlin 8.1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,氟比洛芬的主要药动学参数:AUC_(0-t):(27644.02±6243.692)min·ng·ml^(-1)和(28108.34±5591.35)min·ng·ml^(-1);AUC_(0-∞):(28606.46±6876.76)min·ng·ml^(-1)和(29040.66±6077.13)min·ng·ml^(-1);Cmax:(9349.17±1161.30)ng·ml^(-1)和(9415.42±1228.08)ng·ml^(-1);T_(max)中位数分别为0.07 h和0.05 h。受试制剂和参比制剂的AUC_(0-t),AUC_(0-∞),C_(max)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:国产氟比洛芬酯注射液与原研参比制剂生物等效。

Objective:To establish a method to investigate pharmacokinetics and bioequivalence of domestic flurbiprofen axetil injection.Methods:An open,randomized,and two-cycle crossover study was conducted in 24 healthy volunteers.Plasma concentrations of flurbiprofen were determined by LC-MS/MS after administering a single dose of reference drug or test drug.Main pharmacokinetic parameters were calculated by using Phoenix Win Nonlin(V8.1)software.Results:For the test drug and the reference drug,the main pharmacokinetic parameters of flurbiprofen were as follows:AUC0-twas(27644.02±6243.692)min·ng·ml^(-1) and(28108.34±5591.351)min·ng·ml^(-1),AUC_(0-∞) was(28606.46±6876.757)min·ng·ml^(-1) and(29040.66±6077.130)min·ng·ml^(-1),C_(max) was(9349.17±1161.303)ng·ml^(-1) and(9415.42±1228.077)ng·ml^(-1),and the median of T_(max) was 0.07 h and 0.05 h,respectively.Under two kinds of conditions,90% CIs of AUC_(0-t),AU_(C0-∞) and C_(max) of the test preparation were 80%-125% of the corresponding parameters of the reference preparation,and there was no statistical significance in T_(max) between the two preparations(P>0.05).Conclusion:The test drug and the reference drug are bioequivalent.