Li Dai, Xu Sumei, Wang Yulu, Li Dan, Li Xiaomin, Pan Jing, Xu Pingsheng
National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410008, China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China.
Oncotarget. 2017 Aug 7;8(41):70752-70760. doi: 10.18632/oncotarget.19984. eCollection 2017 Sep 19.
Since angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have complimentary mechanisms of action, enalapril, an ACE inhibitor, is used in combination with felodipine, a vascular selective dihydropyridine calcium antagonist, for the treatment of hypertension. The present study was designed to investigate the possible drug-drug interaction between these two agents in Chinese healthy subjects. A randomized, open-label, multiple-dose, 3-treatment, 3-period, 6-sequence cross-over study enrolling 12 healthy subjects (six male and six female subjects) was performed. Plasma pharmacokinetic studies were performed after 5 mg of enalapril and 5 mg of felodipine were administered alone or concomitantly twice per day for six days, and once in the morning of day seven. All 12 healthy subjects (mean [SD] age, 24.3 [2.8] years; body weight, 57.3 [5.7] kg; height, 163.2 [5.2] cm) completed all scheduled pharmacokinetic studies. Geometric mean ratios (with 90% CIs) of AUC and C for enalapril administered concomitantly with felodipine enalapril administered alone were 1.025 (0.80-1.25) and 1.065 (0.70-1.43), respectively. Geometric mean ratios (with 90% CIs) of AUC and C for felodipine administered concomitantly with enalapril felodipine administered alone were 1.14 (0.97-1.31) and 0.80 (0.65-0.95), respectively. There were no severe or serious drug-related adverse events observed during the study. Our results revealed that the co-administration of enalapril and felodipine affected the pharmacokinetics of felodipine, but not that of enalapril. Although the difference in PK parameters was statistically significant, its clinical significance may be limited, considering safety profile observed in the present study.
由于血管紧张素转换酶（ACE）抑制剂和钙拮抗剂具有互补的作用机制，因此血管紧张素转换酶抑制剂依那普利与血管选择性二氢吡啶类钙拮抗剂非洛地平联合用于治疗高血压。本研究旨在调查这两种药物在中国健康受试者中可能存在的药物相互作用。开展了一项随机、开放标签、多剂量、三治疗组、三周期、六序列交叉研究，纳入12名健康受试者（6名男性和6名女性）。在单独或同时每日两次给予5mg依那普利和5mg非洛地平，持续6天，并在第7天上午给药一次后，进行血浆药代动力学研究。所有12名健康受试者（平均[标准差]年龄，24.3[2.8]岁；体重，57.3[5.7]kg；身高，163.2[5.2]cm）均完成了所有预定的药代动力学研究。依那普利与非洛地平联合给药时依那普利的AUC和C的几何平均比值（90%CI）分别为1.025（0.80 - 1.25）和1.065（0.70 - 1.43）。非洛地平与依那普利联合给药时非洛地平的AUC和C的几何平均比值（90%CI）分别为1.14（0.97 - 1.31）和0.80（0.65 - 0.95）。研究期间未观察到严重或严重的药物相关不良事件。我们的结果显示，依那普利和非洛地平联合给药影响了非洛地平的药代动力学，但未影响依那普利的药代动力学。尽管药代动力学参数的差异具有统计学意义，但考虑到本研究中观察到的安全性，其临床意义可能有限。
