Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Drug Des Devel Ther. 2021 Feb 17;15:651-658. doi: 10.2147/DDDT.S288986. eCollection 2021.
A fixed-dose combination (FDC) of gemigliptin/rosuvastatin 50/20 mg as a monolayer tablet has been used to treat patients with both type 2 diabetes mellitus and dyslipidemia. To improve the stability of the FDC, a new FDC formulation as a bilayer tablet was developed. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the FDC of gemigliptin/rosuvastatin 50/20 mg between the newly developed bilayer tablet and the approved monolayer tablet in healthy subjects.
A randomized, open-label, single-dose, two-treatment, two-way crossover study was conducted. Subjects received a single dose of the FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet or the monolayer tablet in each period with a 7-day washout. For PK and PD analyses, serial blood samples were collected up to 72 hours after dosing to determine plasma concentrations of gemigliptin, its active metabolite LC15-0636 and rosuvastatin, and plasma dipeptidyl peptidase-4 (DPP-4) activity. PK and PD parameters were calculated using non-compartmental methods and compared between the two formulations.
A total of 48 healthy subjects were randomized, and 45 subjects completed the study. The concentration-time profiles of gemigliptin, LC15-0636 and rosuvastatin were comparable between the two formulations. All geometric mean ratios (90% confidence intervals) of the bilayer tablet to the monolayer tablet for maximum plasma concentration and area under concentration-time curve from 0 to last measurable time point of the three compounds fulfilled the bioequivalence criteria of 0.80-1.25. Likewise, area under plasma DPP-4 activity inhibition from baseline-time curve from 0 to last measurable time point and maximum inhibition of plasma DPP-4 activity were similar between the two formulations.
The FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet showed equivalent PK and PD properties with the FDC of gemigliptin/rosuvastatin 50/20 mg as the monolayer tablet in healthy subjects. These results suggest that the newly developed bilayer tablet can become an alternative formulation to the commercially available monolayer tablet.
将固定剂量组合（FDC）的 gemigliptin/rosuvastatin 50/20 毫克制成单层片剂，用于治疗 2 型糖尿病和血脂异常患者。为提高 FDC 的稳定性，开发了一种新的 FDC 双层片剂制剂。本研究旨在比较健康受试者中新型双层片剂和已批准的单层片剂的 gemigliptin/rosuvastatin 50/20 毫克 FDC 的药代动力学（PK）和药效学（PD）。
进行了一项随机、开放标签、单剂量、两治疗、两交叉研究。在每个周期中，受试者接受一次 gemigliptin/rosuvastatin 50/20 毫克 FDC 的双层片剂或单层片剂治疗，洗脱期为 7 天。为了进行 PK 和 PD 分析，在给药后 72 小时内采集连续血样，以确定 gemigliptin、其活性代谢物 LC15-0636 和 rosuvastatin 的血浆浓度以及二肽基肽酶-4（DPP-4）活性。使用非房室方法计算 PK 和 PD 参数，并比较两种制剂之间的参数。
共纳入 48 名健康受试者，45 名受试者完成了研究。两种制剂的 gemigliptin、LC15-0636 和 rosuvastatin 的浓度-时间曲线相似。三种化合物的最大血浆浓度和从 0 到最后可测量时间点的浓度-时间曲线下面积的双层片剂与单层片剂的所有几何均数比值（90%置信区间）均符合 0.80-1.25 的生物等效性标准。同样，从基线时间曲线到最后可测量时间点的血浆 DPP-4 活性抑制面积和最大血浆 DPP-4 活性抑制率在两种制剂之间相似。
健康受试者中，gemigliptin/rosuvastatin 50/20 毫克的 FDC 双层片剂与 gemigliptin/rosuvastatin 50/20 毫克的 FDC 单层片剂具有等效的 PK 和 PD 特性。这些结果表明，新开发的双层片剂可以成为市售单层片剂的替代制剂。
