Poxel SA, 259/261 Avenue Jean Jaurès, 69007, Lyon, France.
Clin Pharmacokinet. 2021 Apr;60(4):485-490. doi: 10.1007/s40262-020-00948-1. Epub 2020 Nov 9.
Imeglimin is a novel oral antidiabetic drug used to treat type 2 diabetes, targeting the mitochondrial bioenergetics. Imeglimin is mainly excreted unchanged by the kidneys and is a substrate of organic cation transporters, which are expressed in the kidney and the liver.
The aim of this study was to assess the effect of hepatic impairment on the pharmacokinetics of imeglimin.
An open-label, single-dose, parallel-group study was carried out in seven subjects with normal hepatic function and seven subjects with moderate hepatic impairment who received a single dose of imeglimin 1000 mg. Blood and urine samples were collected up to 48 h after imeglimin administration. Pharmacokinetics were determined using non-compartmental methods.
Imeglimin maximum observed plasma concentration (C) and area under the plasma concentration-time curve (AUC) in subjects with moderate hepatic impairment was 1.3-fold (90% confidence interval [CI] 1.05-1.60) and 1.5-fold (90% CI 1.19-1.82) higher than in subjects with normal hepatic function, but was not considered as clinically meaningful. Higher plasma exposure and amount of imeglimin renally excreted in moderate hepatic impaired subjects, associated with an unchanged elimination rate, suggests that this increase could be linked to a higher oral absorption and/or lower hepatic uptake in this population.
Imeglimin was safe and well tolerated in all subjects.
EudraCT 2018-001950-83.
依格列净是一种新型的口服降糖药物，用于治疗 2 型糖尿病，作用靶点为线粒体生物能量学。依格列净主要以原形经肾脏排泄，是有机阳离子转运体的底物，该转运体在肾脏和肝脏中表达。
本研究旨在评估肝损伤对依格列净药代动力学的影响。
开展了一项开放标签、单剂量、平行组研究，纳入 7 例肝功能正常受试者和 7 例中度肝损伤受试者，单次口服依格列净 1000mg。给药后 48h 内采集血样和尿样。采用非房室模型法进行药代动力学分析。
中度肝损伤受试者的依格列净最大血药浓度（C）和血药浓度-时间曲线下面积（AUC）分别为肝功能正常受试者的 1.3 倍（90%置信区间：1.05-1.60）和 1.5 倍（90%置信区间：1.19-1.82），但无临床意义。中度肝损伤受试者的血浆暴露量增加，且更多的依格列净经肾脏排泄，消除率无变化，提示这种增加可能与该人群的口服吸收增加和/或肝脏摄取减少有关。
所有受试者均对依格列净耐受良好且安全。
EudraCT 2018-001950-83。
