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Pharmacokinetic/Pharmacodynamic Interactions Between Evogliptin and Glimepiride in Healthy Male Subjects
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-11-24 , DOI: 10.2147/dddt.s275343 Hyounggyoon Yoo 1 , Yun Kim 1 , In-Jin Jang 1 , Kyung-Sang Yu 1 , SeungHwan Lee 1
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2020-11-24 , DOI: 10.2147/dddt.s275343 Hyounggyoon Yoo 1 , Yun Kim 1 , In-Jin Jang 1 , Kyung-Sang Yu 1 , SeungHwan Lee 1
Affiliation
Purpose: Evogliptin, a dipeptidyl peptidase-4 inhibitor, and glimepiride, a sulfonylurea, are used to treat type 2 diabetes mellitus. In this study, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride.
Materials and Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or a combination of the two (EVO+GLI). Serial blood and urine samples were collected 168 and 24 h post dosing, respectively, for PK and PD analyses.
Results: Thirty-four subjects completed the study. The co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (Cmax,ss) and the area under the curve during dosing interval at steady-state (AUCτ,ss) of EVO+GLI to E were 1.02 (0.98– 1.06) and 0.97 (0.95– 1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01– 1.17) and 1.08 (1.02– 1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.8– 1.25. Glucose excursion decreased with the co-administration of evogliptin and glimepiride compared with that observed with the evogliptin or glimepiride monotherapy.
Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while the combination therapy showed an additive glucose-lowering effect compared to those of evogliptin or glimepiride monotherapy.
Keywords: evogliptin, glimepiride, pharmacokinetics, pharmacodynamics, drug interaction
中文翻译：
依格列汀和格列美脲在健康男性受试者中的药代动力学/药效学相互作用
目的： Evogliptin（一种二肽基肽酶 4 抑制剂）和格列美脲（一种磺脲类药物）用于治疗 2 型糖尿病。在本研究中，我们旨在评估 evogliptin 和格列美脲之间的药代动力学 (PK) 和药效学 (PD) 相互作用。
材料和方法：在健康男性受试者中进行了一项随机、开放标签、3 期、3 次治疗、2 序列交叉研究。在每个时期，受试者接受多剂量的 evogliptin 5 mg 单独 (EVO)、格列美脲 4 mg 单独 (GLI) 或两者的组合 (EVO+GLI)。分别在给药后 168 和 24 小时收集系列血液和尿液样本，用于 PK 和 PD 分析。
结果：34 名受试者完成了研究。evogliptin 和格列美脲的共同给药没有改变他们的血浆和尿液 PK 曲线。对于依格列汀，稳态时最大血浆浓度 (C max,ss ) 和稳态给药间隔期间曲线下面积 (AUC τ,ss ) 的几何平均比 (GMR) (90% 置信区间) EVO+GLI 与 E 的比值分别为 1.02 (0.98–1.06) 和 0.97 (0.95–1.00)。对于格列美脲，EVO+GLI 与 GLI 的对应值分别为 1.08 (1.01–1.17) 和 1.08 (1.02–1.14)。所有值均在 0.8-1.25 的监管生物等效性标准范围内。与使用 evogliptin 或格列美脲单药治疗观察到的相比，随着 evogliptin 和格列美脲的共同给药，葡萄糖漂移减少。
结论： Evogliptin 和格列美脲联合用药时没有 PK 相互作用，而联合治疗与 evogliptin 或格列美脲单药治疗相比显示出附加的降糖作用。
【关键词】：依格列汀 格列美脲 药代动力学 药效学 药物相互作用
更新日期：2020-11-25
Materials and Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or a combination of the two (EVO+GLI). Serial blood and urine samples were collected 168 and 24 h post dosing, respectively, for PK and PD analyses.
Results: Thirty-four subjects completed the study. The co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (Cmax,ss) and the area under the curve during dosing interval at steady-state (AUCτ,ss) of EVO+GLI to E were 1.02 (0.98– 1.06) and 0.97 (0.95– 1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01– 1.17) and 1.08 (1.02– 1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.8– 1.25. Glucose excursion decreased with the co-administration of evogliptin and glimepiride compared with that observed with the evogliptin or glimepiride monotherapy.
Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while the combination therapy showed an additive glucose-lowering effect compared to those of evogliptin or glimepiride monotherapy.
Keywords: evogliptin, glimepiride, pharmacokinetics, pharmacodynamics, drug interaction
中文翻译：
依格列汀和格列美脲在健康男性受试者中的药代动力学/药效学相互作用
目的： Evogliptin（一种二肽基肽酶 4 抑制剂）和格列美脲（一种磺脲类药物）用于治疗 2 型糖尿病。在本研究中，我们旨在评估 evogliptin 和格列美脲之间的药代动力学 (PK) 和药效学 (PD) 相互作用。
材料和方法：在健康男性受试者中进行了一项随机、开放标签、3 期、3 次治疗、2 序列交叉研究。在每个时期，受试者接受多剂量的 evogliptin 5 mg 单独 (EVO)、格列美脲 4 mg 单独 (GLI) 或两者的组合 (EVO+GLI)。分别在给药后 168 和 24 小时收集系列血液和尿液样本，用于 PK 和 PD 分析。
结果：34 名受试者完成了研究。evogliptin 和格列美脲的共同给药没有改变他们的血浆和尿液 PK 曲线。对于依格列汀，稳态时最大血浆浓度 (C max,ss ) 和稳态给药间隔期间曲线下面积 (AUC τ,ss ) 的几何平均比 (GMR) (90% 置信区间) EVO+GLI 与 E 的比值分别为 1.02 (0.98–1.06) 和 0.97 (0.95–1.00)。对于格列美脲，EVO+GLI 与 GLI 的对应值分别为 1.08 (1.01–1.17) 和 1.08 (1.02–1.14)。所有值均在 0.8-1.25 的监管生物等效性标准范围内。与使用 evogliptin 或格列美脲单药治疗观察到的相比，随着 evogliptin 和格列美脲的共同给药，葡萄糖漂移减少。
结论： Evogliptin 和格列美脲联合用药时没有 PK 相互作用，而联合治疗与 evogliptin 或格列美脲单药治疗相比显示出附加的降糖作用。
【关键词】：依格列汀 格列美脲 药代动力学 药效学 药物相互作用
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