复方依那普利非洛地平缓释片在健康中国人体内的药动学特征  

Pharmacokinetics of Compound Enalapril-Felodipine Extended Release Tablets in Chinese Healthy Subjects

作　　者：刘善军[1] 周文佳[1] 黄艳[1] 刘筱雪[1] 丁黎[1] 

机构地区：[1]中国药科大学药物分析教研室,江苏南京210009

出　　处：《药学进展》2013年第1期31-38,共8页Progress in Pharmaceutical Sciences

摘　　要：目的:研究复方依那普利非洛地平缓释片在健康中国人体内的药动学特征。方法:采用双交叉实验设计,将12名健康受试者随机分为2组,先接受第1周期低剂量给药,即分别单次口服受试制剂(复方依那普利非洛地平缓释片,每片含非洛地平5 mg和马来酸依那普利5 mg)1片和2种单方参比制剂(马来酸依那普利片,含马来酸依那普利5 mg;非洛地平缓释片,含非洛地平5 mg)各1片,然后分别每日口服受试制剂1片和2种单方参比制剂各1片,连续7 d。第1周期结束后,2组再交叉进行第2周期研究,给药方案同第1周期。随后进行高剂量研究,即2组所有受试者均单次口服受试制剂2片。采用液质联用法测定人血浆中非洛地平、依那普利及其活性代谢物依那普利拉的浓度,计算药动学参数并进行统计学分析。结果:单次低剂量给药研究中,受试者分别口服受试制剂与合用2种单方参比制剂所测得的非洛地平、依那普利和依那普利拉的各药动学参数均无显著差异(P>0.05);多次低剂量给药研究中,除口服受试制剂者的依那普利拉Tmax比口服参比制剂的受试者平均提前0.6 h左右(P<0.05)以外,其他药动学参数均无显著差异(P>0.05);单次低、高剂量给药的药动学数据显示:所有受试者血浆中非洛地平、依那普利和依那普利拉的AUC和Cmax均随给药剂量提高而增大,除接受高剂量受试制剂者的依那普利Tmax较接受低剂量的受试者平均延迟0.4 h左右(P<0.05)以外,两者间的其他药动学参数均无显著差异(P>0.05);各药动学参数在男性和女性受试者间无显著差异(P>0.05)。结论:该研究建立的人血浆中非洛地平、依那普利和依那普利拉的LC-MS测定方法的准确度、精密度、稳定性及线性关系等均符合生物样品的分析要求,适用于复方依那普利非洛地平缓释片人体药动学研究;口服受试制剂与同服2种单方参比制剂的体内药动学过程基�release tablets were randomly 5 mg/enalapril maleate 5 rag） Objective： To study the pharmacokinetics of compound enalapril-felodipine extended in Chinese healthy subjects. Methods： 12 healthy subjects （ half male and half female） divided into 2 groups, and administered the low dose of the test preparations （felodipine maleate 5 mg） and two kinds of reference preparations （felodipine 5 mg ＋ enalapril in a single-dose, then a 7-day multi-dose, under the two-way crossover design. After theabove study, all the subjects were administered the single high dose of the test preparations （ felodipine 10 rag/ enalapril maleate 10 mg）. The concentration of felodipine, enalapril and the active metabolite enalaprilat in human plasma was determined by LC-MS method. The pharmacokinetic parameters were calculated and the related statistical analysis was conducted. Results： In the single low-dose study, the pharmacokinetic parameters of felodipine, enalapril and enalaprilat did not show a statistically significant difference between the subjects administered test preparations and those administered reference prepara- tions （P 〉 0. 05）. In the multiple low-dose study, the pharmacokinetic parameters of felodipine, enalapril and enalaprilat did not show a statistically significant difference （ P 〉 0.05） except that the Tmax of the enalaprilat in subjects administered test preparations was about 0.6 h earlier than that of subjects admi- nistered reference preparations （P 〈 0. 05）. In both of the single low dose and single high dose experi- ments, the AUC and Cmax values of felodipine, enalapril and enalaprilat increased with the increase of the dosage. The pharmacokinetic parameters of felodipine, enalapril and enalaprilat did not show a statistically significant difference （P 〉0. 05） except that the Tmax of the enalapril in the subjects administered high- dose lagged about 0. 4 h compared with that of the subjects administered low-dose （ P 〈 0. 05）. No statisti- cally significant

关 键 词：复方依那普利非洛地平缓释片 依那普利拉 单剂量 多剂量 药动学 液质联用 

分 类 号：R96[医药卫生—药理学]