Drug Clinical Trial Institution, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, China.
J Clin Pharm Ther. 2022 Aug;47(8):1225-1231. doi: 10.1111/jcpt.13659. Epub 2022 Mar 31.
Henagliflozin is a novel selective sodium-glucose co-transporter 2 (SGLT2) inhibitor with similar inhibitory effect to ertugliflozin. Glimepiride is widely used to treat type 2 diabetes mellitus (T2DM) with few cardiovascular side effects. In the present study, we aimed at evaluating the pharmacokinetic (PK) interactions between henagliflozin and glimepiride.
An open-label, single-centre, single-arm, 3-period, 3-treatment, self-control study was conducted in twelve healthy Chinese male subjects. During each study period, subjects received a single oral dose of glimepiride 2 mg, multiple oral doses of henagliflozin 10 mg or a combination of the two drugs. Serial blood samples were collected 24 h post-dosing for PK analyses. Finger-tip blood glucose was also tested for safety evaluation.
Co-administration of henagliflozin with glimepiride did not affect their plasma PK profiles. For henagliflozin, the 90% confidence intervals for the geometric mean ratio (GMR) for the maximum plasma concentrations at steady-state (C ) and the area under the plasma concentration-time curve during a dosing interval at steady-state (AUC ) of combination therapy to henagliflozin alone were 1.00 (0.93-1.08) and 1.00 (0.98-1.02), respectively. For glimepiride, the corresponding values of combination therapy to glimepiride alone were 1.00 (0.88-1.13) for maximum plasma concentrations (C ), 0.91 (0.84-0.99) for the area under the plasma concentration-time curve from 0-24 h (AUC ) and 0.91 (0.83-1.00) for the plasma concentration-time curve from 0 h to infinite (AUC ), respectively. All values fell within the equivalence range of 0.8-1.25. All monotherapies and combination therapy led to no serious adverse events and were well tolerated.
Multiple doses of henagliflozin did not exert a significant change on glimepiride PK profiles and a single dose of glimepiride had little effect on henagliflozin blood concentration. Thus, henagliflozin can be co-administered with glimepiride without dose adjustment of either drug.
Henagliflozin 是一种新型选择性钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂，对依格列净具有相似的抑制作用。格列美脲广泛用于治疗 2 型糖尿病（T2DM），心血管副作用较少。本研究旨在评估 Henagliflozin 与格列美脲之间的药代动力学（PK）相互作用。
本研究采用开放标签、单中心、单臂、3 期、3 种治疗方案、自身对照设计，共纳入 12 例健康中国男性受试者。在每个研究期间，受试者分别单次口服格列美脲 2mg、多次口服 Henagliflozin 10mg 或两种药物联合使用。给药后 24 小时内采集血样进行 PK 分析。还检测指尖血糖以评估安全性。
Henagliflozin 与格列美脲联合使用不影响其血浆 PK 特征。对于 Henagliflozin，联合治疗与单独使用 Henagliflozin 的稳态时最大血浆浓度（C ）和稳态时给药间隔内的血浆浓度-时间曲线下面积（AUC ）的几何均数比值（GMR）的 90%置信区间分别为 1.00（0.93-1.08）和 1.00（0.98-1.02）。对于格列美脲，联合治疗与单独使用格列美脲的相应值分别为 C 处的 1.00（0.88-1.13）、AUC 处的 0.91（0.84-0.99）和 AUC 处的 0.91（0.83-1.00）。所有值均落在 0.8-1.25 的等效范围内。所有单药治疗和联合治疗均未导致严重不良事件，且耐受性良好。
多次给予 Henagliflozin 不会显著改变格列美脲的 PK 特征，单次给予格列美脲对 Henagliflozin 的血药浓度影响不大。因此，无需调整两种药物的剂量即可联合使用 Henagliflozin 和格列美脲。
