比较两种恩格列净制剂在健康韩国受试者中的药代动力学、安全性和耐受性。
Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects.
机构信息
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, USA.
出版信息
Drug Des Devel Ther. 2023 Jul 24;17:2137-2145. doi: 10.2147/DDDT.S409368. eCollection 2023.
PURPOSE
Empagliflozin is a sodium-glucose cotransporter 2 inhibitor that is commonly used for the treatment of type 2 diabetes mellitus. As cocrystal formulation can improve the chemical properties of drugs, CKD-370 was newly developed as a cocrystal formulation of empagliflozin with solvate L-proline. This study aimed to compare the pharmacokinetics, safety, and tolerability of these two empagliflozin formulations in healthy Korean subjects.
METHODS
A randomized, open-label, two-sequence, two-period crossover study was conducted on healthy Korean participants. The subjects received a single oral 25 mg dose of either test (CKD-370) or reference treatment (Jardiance) tablet at each period. Plasma empagliflozin concentrations were determined using liquid chromatography with tandem mass spectrometry. Pharmacokinetic (PK) parameters were analyzed using non-compartmental methods. The primary PK parameters included the maximum concentration (C) and the area under the concentration-time curve from 0 to last (AUC). The safety of both formulations was monitored and evaluated.
RESULTS
A total of 28 healthy Korean adult subjects were randomized, and 27 subjects were included in the PK analysis. The mean ± standard deviation values of the primary PK parameters, C and AUC after administration of the test treatment, were 442.02 ± 103.37 μg/L and 3131.08 ± 529.30 μg·h/L, respectively, and those after administration of the reference treatment were 436.29 ± 118.74 μg/L and 3006.88 ± 514.21 μg·h/L, respectively. The geometric mean ratio and its 90% confidence interval of test to reference treatment for C and AUC were 1.0221 (0.9527-1.0967) and 1.0411 (1.0153-1.0677), respectively, which were within the commonly accepted bioequivalence criteria of 0.80 to 1.25. Both treatments were well-tolerated.
CONCLUSION
The two formulations of empagliflozin showed similar PK characteristics and were generally well tolerated in healthy subjects.
目的
恩格列净是一种钠-葡萄糖共转运蛋白 2 抑制剂，常用于治疗 2 型糖尿病。由于共晶制剂可以改善药物的化学性质，因此新开发了恩格列净与溶剂 L-脯氨酸的共晶制剂 CKD-370。本研究旨在比较这两种恩格列净制剂在健康韩国受试者中的药代动力学、安全性和耐受性。
方法
一项在健康韩国受试者中进行的随机、开放标签、两序列、两周期交叉研究。每个时期，受试者接受单次口服 25mg 受试（CKD-370）或参比治疗（Jardiance）片剂。使用液相色谱-串联质谱法测定血浆恩格列净浓度。使用非房室分析方法分析药代动力学（PK）参数。主要 PK 参数包括最大浓度（C）和从 0 到最后（AUC）的浓度-时间曲线下面积。监测并评估两种制剂的安全性。
结果
共纳入 28 名健康韩国成年受试者，27 名受试者纳入 PK 分析。试验治疗后 C 和 AUC 的主要 PK 参数的平均值±标准差值分别为 442.02±103.37μg/L 和 3131.08±529.30μg·h/L，参比治疗后分别为 436.29±118.74μg/L 和 3006.88±514.21μg·h/L。C 和 AUC 的试验与参比治疗的几何均数比值及其 90%置信区间分别为 1.0221（0.9527-1.0967）和 1.0411（1.0153-1.0677），均在 0.80 至 1.25 的公认生物等效性标准范围内。两种治疗方法均具有良好的耐受性。
结论
两种恩格列净制剂具有相似的 PK 特征，在健康受试者中通常具有良好的耐受性。
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