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

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.