【作者】 朱荣华； 李焕德； 阳剑； 张啟智； 彭文兴；

【Author】 Zhu Ronghua1,2,Li Huande1,Yang Jian1,2,Zhang Qizhi1,2,Peng WenXing1 1. Clinical Pharmacy and Pharmacology Research Institute,Second Xiangya Hospital,Central South University,Changsha 410011 2. School of Pharmacy,Central South University,Changsha 410011

【机构】 中南大学湘雅二医院临床药学研究室； 中南大学药学院；

【摘要】 目的:建立同时测定人血浆中贝那普利及贝那普利拉浓度的UPLC-MS/MS法,研究中国健康志愿者单次口服氨氯地平贝那普利胶囊后贝那普利及其活性代谢物贝那普利拉的药动学特征。方法 :24名健康受试者随机分成3组,每组8人,男女各半,分别单次口服贝那普利含量为10、20、30mg氨氯地平贝那普利胶囊。血浆样品用乙腈进行蛋白沉淀,贝那普利及贝那普利拉的血浆浓度采用超高效液相色谱-串联质谱法检测。结果 :贝那普利及贝那普利拉浓度在1.0-1000.0ng·mL-1范围内线性关系良好。单次口服10、20、30m贝那普利剂量后Tmax分别为0.500.19、0.810.51和0.630.40h;Cmax分别为264.1084.95、376.85173.59和642.42331.14ng·mL-1,AUC0~8分别为245.987.7、450.5122.8和557.673.5ng·h·mL-1,AUC0-∞分别为248.787.9、477.2130.8和580.271.1ng·h·mL-1。t1/2分别为0.760.19、2.851.70和2.911.65h,V/F分别为44.411.5、186.6128.8和217.9122.6L,MRT0~8分别为1.00.3、2.30.7和1.80.6h。CL/F分别为44.514.7、44.611.3和52.57.7L/h;单次口服10、20、30m贝那普利剂量后贝那普利拉的Tmax分别为1.40.5、2.11.3和1.40.4h;Cmax分别为232.60100.46、323.4861.58和615.91188.23ng·mL-1,AUC0~24分别为1025.9172.2、1924.8314.4和3095.1713.4ng·h·mL-1,AUC0-∞分别为1053.6177.1、1989.8320.9和3150.0715.6ng·h·mL-1。t1/2分别为4.90.3、5.00.7和4.30.4h;V/F分别为69.311.5、75.016.5和62.013.8L;CL/F分别为9.71.6、10.31.4和9.92.0L/h;MRT0~24分别为5.91.0、6.71.1和5.50.9h。结论 :所建立的方法灵敏,准确,快捷,适合于贝那普利临床药动学研究。在10-30mg剂量范围内、贝那普利符合线性药动学特征,健康受试者能安全耐受。更多还原

【Abstract】 Objective: To develop a UPLC-MS/MS method for determination of benazepril and benazeprilat in human plasma,and to study the pharmacokinetics of benazepril and benazeprilat in Chinese healthy volunteers.Methods: A single oral dose of 10,20 or 30 mg benazepril in was given to 8 healthy volunteers in an open randomized design.Plasma concentrations of benazepril and benazeprilat were determined by UPLC-MS/MS.Results: The liner range of analysis method was among 1.0-1000.0 ng·mL-1for benazepril and benazeprilat in plasma.The main pharmacokinetic parameters of benazepril after 10,20 and 30 mg dose of benazepril were as follows: Tmax was 0.50 0.19,0.81 0.51 and 0.63 0.40 h;Cmax was 264.10 84.95,376.85 173.59 and 642.42 331.14 ng·mL-1;AUC0~8 was 245.9 87.7,450.5 122.8 and 557.6 73.5 ng·h·mL-1,AUC0-∞ was 248.7 87.9,477.2 130.8 and 580.2 71.1 ng·h·mL-1;t1/2 was 0.76 0.19,2.85 1.70 and 2.91 1.65 h;V/F was 44.4 11.5 、186.6 128.8 and 217.9 122.6 L;MRT0~8 was 1.0 0.3,2.3 0.7 and 1.8 0.6 h;CL/F was 44.5 14.7,44.6 11.3 and 52.5 7.7 L/h.The main pharmacokinetic parameters of benazeprilat after 10,20 and 30 mg dose of benazepril were as follows: Tmax was 1.4 0.5,2.1 1.3 and 1.4 0.4 h;Cmax was 232.60 100.46,323.48 61.58 and 615.91 188.23 ng·mL-1,AUC0~24 was 1025.9 172.2,1924.8 314.4 and 3095.1 713.4 ng·h·mL-1;AUC0-∞ was 1053.6 177.1,1989.8 320.9 and 3150.0 715.6 ng·h·mL-1。t1/2 was 4.9 0.3,5.0 0.7 and 4.3 0.4 h;V/F was 69.3 11.5,75.0 16.5 and 62.0 13.8 L;CL/F was 9.7 1.6,10.3 1.4 and 9.9 2.0 L/h;MRT0~24 was 5.9 1.0、6.7 1.1and 5.5 0.9 h.Conclusion: The established UPLC-MS/MS method was simple,rapid,sensitive and accuracy,and suit for study of clinical benazepril pharmacokinetics.There was linear pharmacokinetics of benazepril and benazeprilat between 10 and 30 mg single oral doses of benazepril in healthy subjects.benazepril was well tolerated and no adverse reaction was observed during the trial.更多还原