Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Department of Clinical Pharmacology, Kyungpook National University Hospital, Daegu, Republic of Korea.
Drug Des Devel Ther. 2020 May 26;14:2101-2111. doi: 10.2147/DDDT.S248205. eCollection 2020.
Fimasartan, an angiotensin II type 1 receptor blocker, and linagliptin, a dipeptidyl-peptidase-4 inhibitor, are frequently coadministered to treat patients with hypertension and diabetes, respectively. This study sought to evaluate the pharmacokinetic interactions between fimasartan and linagliptin after co-administration in healthy Korean subjects.
The overall study was divided into two separate parts, with each part designed as an open-label, multiple-dose, two-period, and single-sequence study. In Part A, to investigate the effect of linagliptin on fimasartan, 25 subjects received 120 mg fimasartan alone once daily for seven days during Period I, and 120 mg fimasartan with 20 mg linagliptin for seven days during Period II. In Part B, to examine the effect of fimasartan on linagliptin, 12 subjects received only linagliptin once daily for seven days during Period I, followed by concomitant administration of fimasartan for seven days during Period II, at the same doses used in Part A. Serial blood samples were collected at scheduled intervals for up to 24 h after the last dose to determine the steady-state pharmacokinetics of both drugs.
Thirty-six subjects completed the study. The geometric mean ratio and 90% confidence intervals for maximum plasma concentration at steady state (C) and area under the concentration-time curve at steady state (AUC) of fimasartan with or without linagliptin were 1.2633 (0.9175-1.7396) and 1.1740 (1.0499-1.3126), respectively. The corresponding values for C and AUC of linagliptin with or without fimasartan were 0.9804 (0.8480-1.1336) and 0.9950 (0.9322-1.0619), respectively. A total of eight adverse events (AEs) were reported and the incidence of AEs did not increase significantly with co-administration of the drugs.
Our results suggest that there are no clinically significant pharmacokinetic interactions between fimasartan and linagliptin when co-administered. Treatments were well tolerated during the study, with no serious adverse effects.
http://clinicaltrials.gov, NCT03250052.
替米沙坦是一种血管紧张素 II 型 1 型受体阻滞剂，利拉利汀是一种二肽基肽酶-4 抑制剂，分别常用于治疗高血压和糖尿病患者。本研究旨在评估健康韩国受试者中替米沙坦和利拉利汀联合用药时的药代动力学相互作用。
整个研究分为两个独立部分，每个部分均设计为开放标签、多剂量、两周期和单序列研究。在第 A 部分中，为了研究利拉利汀对替米沙坦的影响，25 名受试者在第 I 期内每天接受一次 120mg 替米沙坦单药治疗，持续 7 天，在第 II 期内每天接受一次 120mg 替米沙坦和 20mg 利拉利汀治疗，持续 7 天。在第 B 部分中，为了检测替米沙坦对利拉利汀的影响，12 名受试者在第 I 期内每天接受一次利拉利汀单药治疗，持续 7 天，随后在第 II 期内每天同时接受替米沙坦治疗，剂量与第 A 部分相同。在最后一次给药后长达 24 小时内，以预定间隔采集连续血样，以确定两种药物的稳态药代动力学。
36 名受试者完成了研究。替米沙坦与利拉利汀合用或不合用的稳态时最大血浆浓度（C）和稳态时浓度-时间曲线下面积（AUC）的几何均数比值和 90%置信区间分别为 1.2633（0.9175-1.7396）和 1.1740（1.0499-1.3126）。替米沙坦与利拉利汀合用或不合用的利拉利汀 C 和 AUC 的相应值分别为 0.9804（0.8480-1.1336）和 0.9950（0.9322-1.0619）。共报告了 8 例不良事件（AE），且药物联合使用时 AE 的发生率并未显著增加。
我们的结果表明，替米沙坦和利拉利汀联合使用时不存在临床显著的药代动力学相互作用。在研究期间，治疗均耐受良好，无严重不良影响。
