Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Department of Internal Medicine, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Diabetes Obes Metab. 2017 Feb;19(2):294-298. doi: 10.1111/dom.12813. Epub 2016 Nov 24.
Evogliptin is a novel potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of the present study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of evogliptin in participants with renal impairment (RI). An open-label, parallel-group clinical study was conducted in participants with mild, moderate and severe RI and in matched participants with normal renal function (NRF). A single oral 5-mg dose of evogliptin was administered and serial blood and urine samples were obtained to assess the PK and PD characteristics of evogliptin. Baseline urine samples were collected to evaluate endogenous CYP3A metabolic markers. The plasma exposure to evogliptin and degree of DPP-4 activity inhibition increased with decreasing renal function. The mean areas under the concentration-time curves from 0 to 120 hours were increased 1.2-, 1.8- and 1.98-fold in the mild, moderate and severe RI groups, respectively, compared with the NRF group. The levels of CYP3A metabolic markers were lower in the RI group than in the NRF group. The increase in the plasma concentration of evogliptin is unlikely to result in changes in its efficacy or safety, considering the results of previous clinical studies.
依格列净是一种新型强效、选择性二肽基肽酶-4（DPP-4）抑制剂。本研究旨在评估依格列净在肾功能不全（RI）患者中的药代动力学（PK）和药效动力学（PD）特征。在伴有轻度、中度和重度 RI 的患者以及匹配的肾功能正常（NRF）患者中开展了一项开放标签、平行组临床研究。给予单口服 5mg 剂量的依格列净，并采集连续的血样和尿样以评估依格列净的 PK 和 PD 特征。采集基线尿样以评估内源性 CYP3A 代谢标志物。与 NRF 组相比，依格列净的血浆暴露量和 DPP-4 活性抑制程度随着肾功能的降低而增加。与 NRF 组相比，轻度、中度和重度 RI 组的依格列净 0 至 120 小时浓度-时间曲线下面积分别增加了 1.2、1.8 和 1.98 倍。RI 组的 CYP3A 代谢标志物水平低于 NRF 组。考虑到先前临床研究的结果，依格列净血浆浓度的增加不太可能导致其疗效或安全性发生变化。
