Najib Naji M, Idkaidek Nasir, Adel Ayman, Admour Isra', Astigarraga Rafel E B, De Nucci Gliberto, Alam S Mahmood, Dham Ruwayda
International Pharmaceutical Research Centre (IPRC), Amman, Jordan.
Biopharm Drug Dispos. 2003 Oct;24(7):315-20. doi: 10.1002/bdd.368.
The bioequivalence of two brands of enalapril 20 mg tablets was demonstrated in 24 healthy human volunteers after a single oral dose in a randomized cross-over study, conducted at IPRC, Amman, Jordan. Reference (Renitec, MSD, Netherlands) and test (Narapril, Julphar, UAE) products were administered to fasted male volunteers; blood samples were collected at specified time intervals, plasma separated and analysed for enalapril and its active metabolite (enalaprilat) using a validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical Sciences, USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0-infinity), Cmax, Tmax, T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Julphar's Narapril is bioequivalent to Renitec of MSD, Netherlands.
在约旦安曼的IPRC进行的一项随机交叉研究中，对24名健康人类志愿者单次口服20毫克依那普利片的两个品牌后，证明了它们的生物等效性。将参比产品（Renitec，MSD，荷兰）和受试产品（Narapril，Julphar，阿联酋）给予空腹男性志愿者；在指定时间间隔采集血样，分离血浆，并在巴西圣保罗USP生物医学科学研究所的笛卡尔分析单元使用经过验证的LC-MS/MS方法分析依那普利及其活性代谢物（依那普利拉）。根据两种制剂的血浆浓度-时间曲线确定药代动力学参数AUC(0-t)、AUC(0-∞)、Cmax、Tmax、T(1/2)和消除速率常数，并使用FDA推荐的统计模块进行统计学比较，以评估两个品牌之间的生物等效性。方差分析（ANOVA）未显示两种制剂之间有任何显著差异，90%置信区间落在生物等效性的可接受范围内。基于这些统计推断，得出结论：两个品牌表现出可比的药代动力学特征，Julphar的Narapril与荷兰MSD的Renitec生物等效。
