Kim Eunwoo, Park Kyoung Ryun, Jang In-Jin, Yu Kyung-Sang, Lee SeungHwan
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea.
Drug Des Devel Ther. 2019 Nov 13;13:3879-3885. doi: 10.2147/DDDT.S197054. eCollection 2019.
Fixed-dose combination (FDC) of gemigliptin and rosuvastatin may improve medication compliance of patients with comorbid type 2 diabetes and dyslipidemia. Pharmacokinetics (PK), pharmacodynamics (PD), and safety of gemigliptin/rosuvastatin 50/20 mg FDC was compared with a loose combination of individual tablets in healthy subjects.
A randomized, open-label, single-dose, two-period, two-sequence, two-treatment crossover study was conducted. Subjects received FDC or a loose combination of gemigliptin (50 mg) and rosuvastatin (20 mg) during each period, with a 14-day washout. Serial blood samples were collected up to 72 hrs after dosing to measure plasma concentrations of gemigliptin, its active metabolite LC15-0636, and rosuvastatin for PK assessment, and DPP-4 activity for PD assessment. PK and PD parameters were calculated using a non-compartmental method. Safety profiles were evaluated throughout the study.
Thirty-seven subjects completed the study. The concentration-time profiles of gemigliptin, LC15-0636, and rosuvastatin were similar between FDC and loose combination, respectively. For each of the three compounds, the geometric mean ratios (90% confidence interval) of FDC to loose combination for C and AUC fell within the bioequivalence range of 0.8-1.25. Inhibition of DPP-4 activity-time profiles after administration of FDC and loose combination was overlapping, and I and AUEC were similar. Both FDC and the loose combination were well tolerated.
PK, PD, and safety profiles of gemigliptin, its metabolite, and rosuvastatin were similar between FDC and loose combination. The FDC of gemigliptin (50 mg) and rosuvastatin (20 mg) can be used as an alternative to a loose combination, which is expected to improve patient compliance.
吉格列汀与瑞舒伐他汀的固定剂量复方制剂（FDC）可能会提高2型糖尿病合并血脂异常患者的用药依从性。在健康受试者中，对吉格列汀/瑞舒伐他汀50/20 mg FDC的药代动力学（PK）、药效学（PD）及安全性与单片片剂的松散组合进行了比较。
进行了一项随机、开放标签、单剂量、两周期、两序列、两治疗交叉研究。受试者在每个周期接受FDC或吉格列汀（50 mg）与瑞舒伐他汀（20 mg）的松散组合，洗脱期为14天。给药后长达72小时采集系列血样，以测量吉格列汀、其活性代谢物LC15 - 0636及瑞舒伐他汀的血浆浓度用于PK评估，以及DPP - 4活性用于PD评估。使用非房室方法计算PK和PD参数。在整个研究过程中评估安全性。
37名受试者完成了研究。FDC与松散组合之间，吉格列汀、LC15 - 0636及瑞舒伐他汀的浓度 - 时间曲线分别相似。对于这三种化合物中的每一种，FDC与松散组合的C和AUC的几何平均比值（90%置信区间）均落在生物等效性范围0.8 - 1.25内。FDC和松散组合给药后DPP - 4活性 - 时间曲线重叠，I和AUEC相似。FDC和松散组合耐受性均良好。
FDC与松散组合之间，吉格列汀及其代谢物以及瑞舒伐他汀的PK、PD和安全性相似。吉格列汀（50 mg）与瑞舒伐他汀（20 mg）的FDC可作为松散组合的替代方案，有望提高患者依从性。
