The Pharmacokinetic Interaction of Amlodipine and Losartan After Single-Dose of its Compound Tablets in Healthy Chinese Subjects

Objective of this study was to investigate the interaction on the pharmacokinetics of amlodipine, losartan and E3174 after oral administration of the compound amlodipine tablets, amlodipine besylate tablets and losartan potassium tablets with single dose in healthy Chinese subjects. Twelve healthy Chinese subjects (6 males and 6 females), were randomly assigned to three groups and received a single oral dose of compound amlodipine tablets (amlodipine/losartan, 10 mg/100 mg), amlodipine besylate tablets (10 mg), and losartan potassium tablets (100 mg), respectively. The concentrations of amlodipine, lorsartan and EXP 3174 in human plasma were determined at specified time points by HPLC-MS/MS and HPLC-MS method, respectively; the pharmacokinetic parameters were calculated subsequently. The 90% CI of AUC(0-t), AUC(0-infinity), C-max for amlodipine and losartan entirely fall within the no-effect range of 80%similar to 125%. T-max was evaluated by non-parametric tests. All of those were statistically insignificant (p > 0.05). The 90% CI of AUC(0-t), AUC(0-infinity), C-max for EXP 3174 didn't fall in the no-effec range of 80%similar to 125%. The result of variance analysis showed that the difference comes from the individuals (p < 0.02), while there was no significant difference between the two preparations and during the week (p > 0.05). T-max was evaluated by non-parametric tests, and it was statistically insignificant (p > 0.05). So, there was no significant change on the pharmacokinetic characteristics of amlodipine, losartan and EXP 3174 after taking the compound amlodipine tablets compared to single preparations of amlodipine besylate tablets and losartan potassium tablets. Healthy subjects administered compound amlodipine tablets, the exposure of amlodipine and losartan in vivo did not change significantly. There was no significant competitive or inhibitive effect in the process of absorption, distribution and hepatic drug metabolizing enzyme metabolism when amlodipine and losartan were combined together.