瑞巴派特分散片的人体药动学及生物等效性

Pharmacokinetics and Bioequivalence of Rebamipide Dispersible Tablets in Healthy Volunteers

建立了液相色谱-串联质谱法测定健康志愿者口服瑞巴派特分散片(受试制剂)和普通片(参比制剂,膜固思达^(?))后的血药浓度,估算两制剂的药动学参数并评价生物等效性。采用随机、开放、双周期交叉试验设计,22名男性健康志愿者单剂量口服受试或参比制剂0.1 g后,血样经乙腈直接沉淀蛋白后进行LC-MS/MS分析,利用DAS2.1.1软件计算药动学参数,并进行生物等效性评价。受试和参比制剂在人血浆中瑞巴派特的c_(max)为(236.9±l 03.4)和(233.9±105.1)ng/ml,t_(max)为(2.7±1.1)和(2.9±1.4)h,t_(1/2)为(2.0±0.8)和(2.3±1.5)h,AUC_(0→12h)为(929.0±291.9)和(970.5±353.2)ngh·ml^(-1)。受试制剂的相对生物利用度为(102.6±29.8)%。

An LC-MS/MS method was established for the determination of rebamipide in human plasma to evaluate the pharmacokinetics and bioequivalence of rebamipide dispersible tablets （test preparation） in healthy volunteers. A single oral dose of two rebamipide preparations [test tablets vs. commercial tablets （Mucosta）, reference preparation] was given to 22 healthy male volunteers according to a randomized crossover design. Drug plasma concentrations were determined by LC-MS/MS after deproteinized with acetonitrile. The pharmacokinetic parameters were calculated by DAS2.1.1 software. The main pharmacokinetic parameters of rebamipide in test and reference preparations were as follows： Cmax（236.9±103.4） and （233.9±105.1） ng/ml, tmax（2.7±1.1） and （2.9±1.4）h, t1/2（2.0±0.8） and （2.3±1.5）h, AUC0-12 h（929.0±291.9） and （970.5±353.2）ng·h·ml^-1 respectively. The relative bioavailability of test formulation was （102.6±29.8） %.