Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor, Coadministered with Sitagliptin in Healthy Volunteers
Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor, Coadministered with Sitagliptin in Healthy Volunteers
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DOI：
10.1007/s12325-012-0055-3
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发表时间：
2012-10-01
影响因子：
3.8
通讯作者：
Woerle, Hans J.
中科院分区：
文献类型：
--
作者：
Brand, Tobias;Macha, Sreeraj;Woerle, Hans J.
这项随机、开放标签、交叉研究调查了葡萄糖共转运蛋白-2 （SGLT-2）抑制剂恩格列净和二肽基肽酶-4 （DPP-4）抑制剂西格列汀之间潜在的药物-药物相互作用。恩格列净是一种有效的选择性SGLT-2抑制剂，通过抑制肾葡萄糖重吸收降低血糖水平，导致尿糖排泄增加。西格列汀通过胰岛素依赖的作用机制降低血糖。16名健康男性志愿者接受了三种治疗（A， B， C），两种治疗顺序（AB + C，或C + AB）中的一种。在治疗AB中，每天给药50mg恩帕列净一次（每日一次），持续5天（治疗A），紧接着联合给药50mg恩帕列净一次，100mg西格列汀一次，持续5天（治疗B）。C组给予西格列汀100 mg，每日一次，连续5天。洗脱期为千分之一，分别为AB组和c组，分别为7天。西格列汀与恩格列净合用在均匀给药间隔tau （AUC(tau,ss)）稳定状态下血浆中分析物的浓度-时间曲线下面积无临床相关影响(几何平均比[GMR] 110.4；90%置信区间[CI] 103.9, 117.3)或均匀给药间隔内稳定状态下血浆中分析物的最大测量浓度（C (max,ss)） （GMR 107.6; 90% CI 97.0, 119.4）。恩格列净与西格列汀合用对西格列汀的AUC(tau,ss) （GMR 103.1; 90% CI 98.9, 107.3）或C(max,ss) （GMR 108.5; 90% CI 100.7, 116.9）没有临床意义的影响。恩帕列净和西格列汀单独或联合用药耐受性良好。5名受试者（31.3%）报告了至少一次不良事件（AE）： 3名受试者（18.8%）在接受恩格列净单药治疗时发生了AE， 3名受试者（18.8%）在接受西格列汀单药治疗时发生了AE。共给药期间无不良事件报告。研究者未发现与药物相关的不良反应。这些结果表明，恩格列净和西格列汀可以在不调整剂量的情况下共同给药。
This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion. Sitagliptin lowers blood glucose through an insulin-dependent mechanism of action.Sixteen healthy male volunteers received three treatments (A, B, C) in one of two treatment sequences (AB then C, or C then AB). In treatment AB, 50 mg empagliflozin was administered once daily (q.d.) for 5 days (treatment A), immediately followed by coadministration of 50 mg empagliflozin q.d. and 100 mg sitagliptin q.d. over 5 days (treatment B). In treatment C, 100 mg sitagliptin was administered q.d. for 5 days. A washout period of a parts per thousand yen7 days separated treatments AB and C.Coadministration of sitagliptin with empagliflozin did not have a clinically relevant effect on the area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval tau (AUC(tau,ss)) (geometric mean ratio [GMR] 110.4; 90% confidence interval [CI] 103.9, 117.3) or maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval tau (C (max,ss)) (GMR 107.6; 90% CI 97.0, 119.4) of empagliflozin. Coadministration of empagliflozin with sitagliptin did not have a clinically meaningful effect on the AUC(tau,ss) (GMR 103.1; 90% CI 98.9, 107.3) or C (max,ss) (GMR 108.5; 90% CI 100.7, 116.9) of sitagliptin. Empagliflozin and sitagliptin were well tolerated when given alone or in combination. Five subjects (31.3%) reported at least one adverse event (AE): three (18.8%) experienced an AE while receiving empagliflozin monotherapy and three (18.8%) while receiving sitagliptin monotherapy. No adverse events were reported during the coadministration period. No AEs were regarded as drug-related by the investigator.These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments.