复方苯磺酸氨氯地平/阿托伐他汀钙片的人体药动学

Pharmacokinetics of amlodipine besylate/atorvastatin calcium combination tablet in healthy volunteers

目的:研究复方苯磺酸氨氯地平/阿托伐他汀钙片中氨氯地平和阿托伐他汀钙在健康人体的药动学特征。方法:30名健康志愿者随机分成3组,每组10名(男女各半),分别单次空腹口服不同规格的受试药品复方苯磺酸氨氯地平/阿托伐他汀钙片,规格分别为5mg/10mg/片,10mg/10mg/片,5mg/20mg/片各1片,采用液相色谱串联质谱方法(LC-MS/MS)研究2种成分的血药浓度经时过程,计算相应的药动学参数,并评价复方苯磺酸氨氯地平/阿托伐他汀钙片在人体的药动学特征。结果:氨氯地平5mg/10mg/片剂量组中的药动学参数分别为Cmax为(3.1±0.5)μg.L-1,AUC0-120为(131±22)μg.h.L-1;10mg/10mg/片剂量组,Cmax为(6.8±1.2)μg.L-1,AUC0-120为(327±110)μg.h.L-1;5mg/20mg/片剂量组,Cmax为(3.1±0.5)μg.L-1,AUC0-120为(130±16)μg.h.L-1。阿托伐他汀5mg/10mg/片剂量组中的药动学参数分别为Cmax为(11.3±6.7)μg.L-1,AUC0-120为(133.8±93.3)μg.h.L-1;10mg/10mg/片剂量组,Cmax为(16.7±12.1)μg.L-1,AUC0-120为(107.7±60.4)μg.h.L-1;5mg/20mg/片剂量组,Cmax为(15.0±9.4)μg.L-1,AUC0-120为(147.3±59.3)μg.h.L-1。结论:复方苯磺酸氨氯地平/阿托伐他汀钙片中氨氯地平的Cmax,AUC0-120,AUC0-∞与剂量呈线性;阿托伐他汀的Cmax,AUC0-120,AUC0-∞与剂量呈非线性药动学特征。

OBJECTIVE To study the pharmacokinetics of combination tablets containing amlodipine besylate/atorvastatin calcium in healthy volunteers. METHODS Thirty healthy volunteers（half male - half female）were divided into three groups. Each ten volunteers received a different dose strengths combination tablets （amlodipine/atorvastatin 5 mg/ 10 mg, 10 mg/ 10 mg,5 mg/20 mg）, respectively. The plasma concentrations of amlodipine and atorvastatin were measured by a fully validated LC-MS/MS method. The pharmacokinetic parameters were calculated thereafter in order to study the pharmacokinetic charateristics of amlodipine and atorvastatin in human. RESULTS The following data were the main pharrnacokinetic parameters. Amlodipine（5 mg/ 10 mg）, Cmax（3.14 ± 0. 46）μg·L^-1 ,AUC0-120 （131 ± 22） ; 10 mg/10 mg,Cmax （6. 85 ± 1.17）μg·L^-1 ,AUC0-120 （327± 110）μg·h·L^-1;5mg/20 mg,Cmax （3.11±0. 47）μg·L^-1 ,AUC0-120 （130± 16）μg·h·L^-1 ; atorvastatin,5 mg/10 mg, Cmax （11.3 ± 6. 7）nμg·L^-1 ,AUC0-120 （133.8 ± 93.3） ;10 mg/10 mg,Cmax （16. 7 ± 12. 1）μg·mL^-1 , AUC0-120 （107. 7 ± 60. 4）μg·h·L^-1 ;5 mg/20 mg,Cmax（15.0 ± 9. 4）μg·L^-1 ,AUC0-120 （147. 3 ± 59. 3）μg·h·L^-1. CONCLUSION In all the three dose groups, Cmax and AUC of amlodipine increased in a dose-dependent manner. Atorvastatin coincide with non-linear pharmacokinetic characteristics.