Yong Xiaolan, Wen Aidong, Liu Xiangyang, Liu Haiyan, Liu Yan-Ping, Li Nan, Hu Tingting, Chen Ying, Wang Minquan, Wang Lantian, Dai Xiaojiao, Huang Juan, Li Jia, Shen Huaqiong
Clinical Pharmacy Lab, General Hospital of Chengdu Military Region PLA, Chengdu, Sichuan, China.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, Shanxi, China.
Clin Drug Investig. 2016 Mar;36(3):195-202. doi: 10.1007/s40261-015-0366-7.
Henagliflozin, a selective inhibitor of the renal sodium glucose cotransporter-2, was developed for type 2 diabetes mellitus (T2DM). This study characterized single- and multiple-dose pharmacokinetics and pharmacodynamics of henagliflozin in Chinese patients with T2DM.
Thirty T2DM patients were randomized in a 4:1 ratio to orally receive either henagliflozin 5, 10, 20 mg/day or placebo for 10 days, except on day 2 and day 3. Pharmacokinetic and pharmacodynamic profiles were measured on day 1 and day 10.
Henagliflozin exhibited dose-proportional plasma concentrations with a half-life ranging from 9.1 to 14 h. Steady-state plasma henagliflozin concentration was reached by day 7 in all active treatment groups. Henagliflozin decreased the 24-h mean plasma glucose by -0.3, -1.0 and -1.0 mmol/L with doses of 5, 10 and 20 mg on day 1, respectively. The corresponding values on day 10 were -0.8, -0.9 and -1.2 mmol/L. Twenty-four-hour urinary glucose excretion increased by 11, 65 and 82 times with doses of 5, 10 and 20 mg on day 1, respectively, with a similar trend on day 10. No treatment-related serious adverse events or discontinuations due to adverse events occurred.
The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients.
恩格列净是一种肾钠葡萄糖协同转运蛋白2的选择性抑制剂，用于治疗2型糖尿病（T2DM）。本研究对恩格列净在中国T2DM患者中的单剂量和多剂量药代动力学及药效学进行了表征。
30例T2DM患者按4:1的比例随机分组，除第2天和第3天外，口服给予恩格列净5、10、20mg/天或安慰剂，共10天。在第1天和第10天测量药代动力学和药效学参数。
恩格列净的血浆浓度呈剂量比例关系，半衰期为9.1至14小时。所有活性治疗组在第7天达到稳态血浆恩格列净浓度。第1天，恩格列净5、10和20mg剂量分别使24小时平均血浆葡萄糖降低-0.3、-1.0和-1.0mmol/L。第10天的相应值分别为-0.8、-0.9和-1.2mmol/L。第1天，恩格列净5、10和20mg剂量使24小时尿糖排泄分别增加11、65和82倍，第10天有类似趋势。未发生与治疗相关的严重不良事件或因不良事件导致的停药。
观察到的恩格列净药代动力学和药效学参数支持在中国T2DM患者中每日一次给药方案。
