布洛芬缓释混悬液空腹和餐后给药的人体生物等效性研究

Study on Bioequivalence of Ibuprofen Sustained-Release Suspension in Fasting and Fed

目的：研究健康受试者空腹和餐后两种状态下单剂量口服布洛芬缓释混悬液受试制剂与参比制剂的生物等效性。方法：本研究包括两个随机、开放、双周期、单剂量给药试验,各入组24名健康受试者,分别空腹和餐后单剂量交叉口服600 mg（20 ml）布洛芬混悬液受试制剂与参比制剂,采用液相色谱-串联质谱（LC-MS/MS）法测定给药后血浆中布洛芬的浓度。结果：空腹给药条件下受试制剂与参比制剂的主要药动学参数中t1/2分别为（4.27±1.42）和（3.87±1.03）h;tmax分别为（3.42±0.72）和（3.29±0.93）h;cmax分别为（27.4±4.33）和（28.2±4.65）μg/ml;AUC0-t分别为（167±30.1）和（172±28.8）μg·h/ml;受试制剂的相对生物利用度为（97.4±9.7）%。餐后给药条件下受试制剂与参比制剂的主要药动学参数中t1/2分别为（2.53±0.46）和（2.64±0.53）h;tmax分别为（3.63±0.99）和（3.44±1.15）h;cmax分别为（25.0±4.12）和（27.0±4.60）μg/ml;AUC0-t分别为（172±33.4）和（184±30.2）μg·h/ml;受试制剂的相对生物利用度为（93.1±5.7）%。两种给药条件下的受试制剂与参比制剂AUC0-t和cmax几何均值比的90%置信区间（CI）均落在80%~125%之间。结论：布洛芬缓释混悬液受试制剂与参比制剂在空腹和餐后两种状态下均具有生物等效性。

OBJECTIVE： To evaluate the bioequivalence of lbuprofen Sustained-Release Suspension test preparation and reference preparation after single oral dose in fasting and fed. METHODS： This study included two randomized, open and , cross-overdouble-cycle and single dose trails, 24 healthy subjects in each group, were single oral administered 600 mg （20 ml） Ibuprofen Sustained-Release Suspension in fasting or fed respectively, plasma concentration of ibuprofen was determined by LC-MS/MS. RESULTS： The t1/2 of test and reference preparation in fasting administration was （4.27 ± 1.42） and （3.87 ± 1.03） h, tmax was （3.42 ± 0.72） and （3.29±0.93） h, Cmax was（27.4±4.33） and （28.2 ±4.65） pg/ml, AUC0-t was （167±30.1） and （172 ±28.8） μtg·h/ml, respectively; the relative bioavailability of test preparation was （97.4 ± 9.7） %. the t1/2 of test and reference preparation in fed administration was （2.53 ± 0.46） and （2.64 ± 0.53） h, tmax was （3.63± 0.99） and （3.44 ± 1.15） h, Cmax was （25.0 ±4.12） and （27.0± 4.60） μg/ml, AUC0-t was （172±33.4） and （184± 30.2） μg·h/ml, respectively; the relative bioavailability of test preparation was （93.1 ±5.7） %. There were 90% CI of test preparation and reference preparation AUC0-t and Cmax geometric mean ratio failed between 80 % - 125 % both in two administration condition. CONCLUSIONS： Ibuprofen Sustained-Release Suspension test preparation bioequivalent to reference preparation both in fasting and fed.