在健康受试者中，钠-葡萄糖共转运蛋白 2 抑制剂恩格列净与过氧化物酶体增殖物激活受体-γ 激动剂罗格列酮之间无相关的药代动力学药物相互作用。
No Relevant Pharmacokinetic Drug-Drug Interaction Between the Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin and Lobeglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, in Healthy Subjects.
机构信息
Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheongju, Republic of Korea.
Department of Pharmacology and Clinical Pharmacology, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Republic of Korea.
出版信息
Drug Des Devel Ther. 2021 Apr 28;15:1725-1734. doi: 10.2147/DDDT.S302215. eCollection 2021.
PURPOSE
Combination therapy with insulin-independent sodium-glucose cotransporter 2 inhibitors and thiazolidinedione drugs, such as lobeglitazone, has been reported to elicit potential additive efficacy in glycemic control in type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetic (PK) drug-drug interactions between empagliflozin and lobeglitazone in healthy subjects.
SUBJECTS AND METHODS
A randomized, open-label, multiple-dose study was conducted in 30 healthy subjects using a three-treatment, six-sequence, three-way crossover design. Subjects received one of the following treatments once daily for 5 days in each period: 25 mg empagliflozin, 0.5 mg lobeglitazone sulfate, or a combination. Serial blood sampling before every dose and up to 24 h after the last dose was performed during each treatment period. The PK parameters were estimated using noncompartmental methods with the plasma empagliflozin and lobeglitazone concentrations. The absence of a PK interaction was construed as the 90% confidence interval (90% CI) of maximum concentration at steady state (C) and area under the concentration-time curve over the dosing interval (AUC) for combination therapy-to-monotherapy ratios within the limits of 0.80-1.25.
RESULTS
The steady-state plasma empagliflozin and lobeglitazone concentration-time profiles of combination therapy and monotherapy were comparable in the 25 subjects who completed the study. Coadministration of empagliflozin with lobeglitazone did not affect empagliflozin PK (with 90% CIs of 0.956-1.150 and 0.945-1.133 for C and AUC, respectively). Likewise, empagliflozin did not affect lobeglitazone C or AUC (with 90% CIs of 0.869-0.995 and 0.851-1.018, respectively). All treatment groups tolerated mild adverse events well.
CONCLUSION
The lack of PK interactions between lobeglitazone and empagliflozin in combination therapy, along with their good tolerability, indicates that the two drugs can be coadministered without dose adjustment.
TRIAL REGISTRATION NUMBER
NCT02854748, Registered on August 7, 2016.
目的
胰岛素非依赖性钠-葡萄糖协同转运蛋白 2 抑制剂与噻唑烷二酮类药物（如罗格列酮）联合治疗 2 型糖尿病，已被报道在血糖控制方面具有潜在的增效作用。本研究旨在评估健康受试者中依帕列净与罗格列酮之间的药代动力学（PK）药物相互作用。
方法
采用三治疗、六序列、三交叉设计，对 30 名健康受试者进行了一项随机、开放标签、多剂量研究。每个周期的 5 天内，受试者每日接受以下一种治疗：25mg 依帕列净、0.5mg 罗格列酮硫酸酯或联合用药。在每个治疗期间，每次给药前和最后一次给药后 24 小时内进行连续血样采集。采用非房室法估算血浆依帕列净和罗格列酮浓度的 PK 参数。如果组合治疗-单药治疗的最大稳态浓度（C）和给药间隔内浓度-时间曲线下面积（AUC）比值的 90%置信区间（90%CI）在 0.80-1.25 范围内，则推断不存在 PK 相互作用。
结果
在完成研究的 25 名受试者中，联合治疗和单药治疗的稳态血浆依帕列净和罗格列酮浓度-时间曲线相似。依帕列净与罗格列酮联合给药不影响依帕列净的 PK（C 和 AUC 的 90%CI 分别为 0.956-1.150 和 0.945-1.133）。同样，依帕列净也不影响罗格列酮 C 或 AUC（C 和 AUC 的 90%CI 分别为 0.869-0.995 和 0.851-1.018）。所有治疗组均耐受轻度不良事件。
结论
联合治疗中罗格列酮与依帕列净之间无 PK 相互作用，且具有良好的耐受性，表明两种药物可以联合使用而无需调整剂量。
临床试验注册号
NCT02854748，注册日期：2016 年 8 月 7 日。
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