复方苯磺酸氨氯地平/盐酸贝那普利片人体药动学研究

Pharmacokinetics of Amlodipine Besylate/Benazepril Hydrochloride Combination Tablets in Healthy Volunteers

关键词:  复方苯磺酸氨氯地平/盐酸贝那普利片  药动学  液质联用  氨氯地平  贝那普利  贝那普利拉

Key words:  amlodipine besylate/benazepril hydrochloride combination tablets  pharmacokinetics  LC-MS/MS  amlodipine  benazepril  benazeprilat

摘要:

目的 研究健康受试者单剂量与多剂量口服复方苯磺酸氨氯地平/盐酸贝那普利片后的药动学。 方法 LC-MS/MS测定单剂量与多剂量给药后氨氯地平与贝那普利及贝那普利拉血药浓度并利用DAS软件计算药动学参数。结果 单剂量给药氨氯地平与贝那普利及贝那普利拉的主要药动学参数分别是：t_1/2为(47.3±10.6)，(1.3±0.4)和(4.5±0.6) h，C_max为(6.4±1.5)，(136.5±40.2)和(158.3±46.7)μg·L^-1，AUC_0-t为(267.7±88.4)，(144.3±46.7)和(891.4±265.4)μg·h·L^-1；多剂量给药氨氯地平与贝那普利的主要药动学参数分别是：t_1/2为(45.1±8.7)，(1.4±0.4)和(5.3±0.8)h，C_max为(8.2±1.8)，(142.4±47.5)和(165.2±40.8)μg·L^-1，AUC_0-t为(413.5±102.4)，(155.7±52.8)和(915.7±316.9)μg·h·L^-1，R为(1.6±0.6)、(1.0±0.1)和(1.2±0.1)。结论 复方苯磺酸氨氯地平/盐酸贝那普利片2组分及活性代谢产物在健康受试者体内的吸收速率和消除速度不随连续给药变化，但连续给药后苯磺酸氨氯地平在体内有轻微蓄积。

Abstract:

OBJECTIVE The pharmacokinetics of amlodipine besylate and benazepril hydrochloride was investigated in male healthy volunteers after single and multiple administrations of amlodipine besylate/benazepril hydrochloride combination tablets. METHODS Concentrations of amlodipine, benazepril and benazeprilat were determined by LC-MS/MS and the pharmacokinetic parameters were calculated with software DAS. RESULTS The pharmacokinetic parameters of amlodipine, benazepril and benazeprilat from single-dose study were as follows: t_1/2 were (47.3±10.6), (1.3±0.4) and (4.5±0.6)h, C_max were (6.4±1.5), (136.5±40.2) and (158.3±46.7)μg·L^-1, AUC_0-t were (267.7±88.4), (144.3±46.7) and (891.4±265.4)μg·h·L^-1, respectively. The pharmacokinetic parameters of amlodipine, benazepril and benazeprilat from multiple-dose study were as follows: t_1/2 were (45.1±8.7), (1.4±0.4) and (5.3±0.8)h，C_max were (8.2±1.8), (142.4±47.5) and (165.2±40.8)μg·L^-1, AUC0-t were (413.5±102.4), (155.7±52.8) and (915.7±316.9)μg·h·L^-1, R were (1.6±0.6), (1.0±0.1) and (1.2±0.1), respectively. CONCLUSION The results suggested that the absorption and elimination rates of amlodipine, benazepril and benazeprilat were not changed after multiple oral administrations, but there was slight accumulation of amlodipine besylate in plasma found after repeated administration.