美洛昔康片在中国健康志愿者空腹和进食条件下的生物等效性研究

Bioequivalence of meloxicam tablets under fasting and fed conditions in Chinese healthy volunteers

目的:评价国产美洛昔康片与进口美洛昔康片在中国健康志愿者空腹和进食条件下的生物等效性。方法:采用开放、均衡、单剂量、双周期、随机交叉设计,分为空腹和进食2种条件。每种条件下各有28名健康志愿者随机分为2组,单剂量口服美洛昔康片受试制剂(T)或参比制剂(R)7.5 mg,验证的液相色谱-串联质谱法测定血浆中美洛昔康的浓度。血药浓度数据采用Phoenix^TM WinNonlin■软件(PharsightCorporation,6.4)进行药动学参数的计算和统计分析。安全性统计分析采用SAS 9.4版本软件进行计算分析。结果:空腹条件下,美洛昔康受试制剂与参比制剂的Cmax分别为(910.68±200.09)和(814.79±201.37)ng·mL^-1,Tmax分别为3.98[1.98,9.98]和3.98[3.48,10]h,t1/2分别为(8.23±1.12)和(21.11±5.35)h,AUC0-t分别为(4.06±1.10)和(3.91±1.05)ng·h·mL^-1;AUC0-∞分别为(4.14±1.15)和(3.98±1.10)ng·h·mL^-1。进食条件下,美洛昔康受试制剂与参比制剂的Cmax分别为(782.22±81.11)和(764.07±75.80)ng·mL^-1,Tmax分别为4.48[2.98,11.98]和4.48[2.98,12]h,t1/2分别为(22.07±7.63)和(21.76±6.40)h,AUC0-t分别为(23633.57±6679.73)和(23863.75±6051.74)ng·h·mL^-1;AUC0-∞分别为(25525.13±9076.08)和(25584.87±7676.27)ng·h·mL^-1。受试制剂与参比制剂空腹和餐后状态下的Cmax,AUC0-t,AUC0-∞的T∶R比值的90%置信区间均在80.00%~125.00%等效区间内。结论:国产美洛昔康片与进口美洛昔康片在中国健康志愿者空腹和进食条件下均具有生物等效性。

Objective:To evaluate the bioequivalence of meloxicam tablets under fasting and fed conditions in Chinese healthy volunteers.Methods:An open,balanced,single-dose,double-cycle,randomized and crossover design was adopted,28 healthy volunteers were randomly divided into two groups under each fasting and fed condition.They were administered a single dose of 7.5 mg meloxicam test tablets(T)or reference tablets(R)orally.The plasma concentrations of meloxicam were determined by a validated high performance liquid chromatography-mass spectrometry method.The pharmacokinetic parameters were calculated and statistically analyzed with PhoenixTM Winnonlinsoftware(Pharsight■Corporation,6.4).The software of SAS 9.4 was used for safety statistical analysis.Results:Under fasting condition,the Cmax of meloxicam test tablets and reference tablets were(910.68±200.09)and(814.79±201.37)ng·mL^-1;Tmax were(3.98[1.98,9.98])and(3.98[3.48,10])h;t1/2 were(21.26±5.56)and(21.11±5.35)h;AUC0-t were(25440.82±5799.43)and(24572.04±5766.93)ng·h·mL^-1;AUC0-∞were(26832.85±7099.21)and(25810.89±6796.60)ng·h·mL^-1.Under fed condition,the Cmax of meloxicam test tablets and reference tablets were(782.22±81.11)and(764.07±75.80)ng·mL^-1;Tmax were(4.48[2.98,11.98])and(4.48[2.98,12])h;t1/2 were(22.07±7.63)and(21.76±6.40)h;AUC0-t were(23633.57±6679.73)and(23863.75±6051.74)ng·h·mL^-1,respectively;AUC0-∞were(25525.13±9076.08)and(25584.87±7676.27)ng·h·mL^-1.The 90%confidence intervals of the T∶R ratios of Cmax,AUC0-t and AUC0-∞were all within the equivalent interval of 80.00%~125.00%.Conclusion:Domestic meloxicam tablets and imported meloxicam tablets are bioequivalent in Chinese healthy volunteers under fasting and fed conditions.