Institute of Clinical Pharmacology and Toxicology, CharitéCentrum für Therapieforschung, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Fundam Clin Pharmacol. 2009 Dec;23(6):767-74. doi: 10.1111/j.1472-8206.2009.00720.x. Epub 2009 Jul 31.
The aim of this study was to investigate any influence on olmesartan plasma pharmacokinetics from amlodipine or atenolol. We analysed pharmacokinetics and safety of olmesartan medoxomil in combination with either amlodipine or atenolol compared to respective monotherapies in two separate studies. In one study, 18 subjects received once daily treatment for 7 days with olmesartan medoxomil 20 mg alone or with amlodipine 5 mg or amlodipine 5 mg alone. In the other study, atenolol 50 mg once daily replaced amlodipine. Concentration vs. time profiles for olmesartan monotherapy were similar to combination therapy. Mean olmesartan AUC(ss,tau) for olmesartan alone and with amlodipine were 2439 and 2388 ng h/mL and for olmesartan alone and with atenolol were 2340 and 2247 ng h/mL. Corresponding olmesartan C(ss,max) values were 465.7 and 439.5 ng/mL for amlodipine, and 447.4 and 423.8 ng/mL for atenolol. Median t(max) values for olmesartan were 1.5 h for each group in each study. Bioequivalence was established for all pharmacokinetic parameters. Lack of significant pharmacokinetic interactions between olmesartan and amlodipine or atenolol provides a basis for combination therapy.
本研究旨在探讨氨氯地平和阿替洛尔对奥美沙坦血浆药代动力学的影响。我们分析了奥美沙坦酯与氨氯地平或阿替洛尔联合用药与相应单药治疗在两项独立研究中的药代动力学和安全性。在一项研究中，18 名受试者接受奥美沙坦酯 20mg 单药治疗或与氨氯地平 5mg 或氨氯地平 5mg 联合治疗，每天一次，连续 7 天。在另一项研究中，每天一次的阿替洛尔 50mg 替代了氨氯地平。奥美沙坦单药治疗的浓度-时间曲线与联合治疗相似。奥美沙坦单独治疗和与氨氯地平联合治疗的奥美沙坦 AUC(ss,tau)分别为 2439 和 2388ng·h/mL，奥美沙坦单独治疗和与阿替洛尔联合治疗的 AUC(ss,tau)分别为 2340 和 2247ng·h/mL。相应的奥美沙坦 C(ss,max)值分别为 465.7 和 439.5ng/mL 用于氨氯地平，以及 447.4 和 423.8ng/mL 用于阿替洛尔。在每个研究中，奥美沙坦的中位数 t(max)值均为 1.5h。所有药代动力学参数均具有生物等效性。奥美沙坦与氨氯地平和阿替洛尔之间不存在明显的药代动力学相互作用，为联合治疗提供了依据。
