PDF(Pubmed)
Abstract：
A fixed-dose combination (FDC) of gemigliptin/metformin can improve the medication adherence in patients with type 2 diabetes mellitus (T2DM). In this study, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of gemigliptin and metformin were compared between FDC and the corresponding loose combination under fasted and fed states. A two-part, randomized, open label, single-dose, two-way crossover study was conducted in healthy male subjects. Under fasted (part 1) or fed (part 2) state, 2 FDC tablets of gemigliptin/metformin sustained release (SR) 25/500 mg or loose combination with one tablet of gemigliptin 50 mg and two tablets of metformin extended release (XR) 500 mg were orally administered in each period with a 7-day washout. Serial blood samples were collected up to 48 hours to determine the drug concentration and the dipeptidyl peptidase 4 (DPP-4) activity. The concentration-time profiles of gemigliptin and metformin were similar between FDC and loose combination in both the fasted and fed states. Geometric mean ratios and 90% confidence intervals of FDC to loose combination for area under the concentration-time curve and maximum plasma concentration of gemigliptin and metformin were within the bioequivalence range (0.8-1.25) in both states. DPP-4 activity-time profiles of FDC were comparable to that of the loose combination, showing similar area under the DPP-4 inhibition-time curve and maximum DPP-4 inhibition between FDC and loose combination, regardless of the fasted or fed state. In conclusion, the PK/PD characteristics of gemigliptin and metformin were similar in FDC tablets and loose combination both in fasted and fed states.
BACKGROUND: ClinicalTrials.gov Identifier: NCT03355014.
BACKGROUND: ClinicalTrials.gov Identifier: NCT03355014.
摘要：
吉格列汀/二甲双胍固定剂量联合用药(FDC)可提高2型糖尿病(T2DM)患者的用药依从性。在这项研究中,在禁食和进食状态下,比较了吉格列汀和二甲双胍的药代动力学(PK)和药效学(PD)谱.两部分，随机化，开放标签,单剂量,在健康男性受试者中进行了双向交叉研究.在紧固（第1部分）或喂食（第2部分）状态下，在每个时期口服给予2片FDC吉格列汀/二甲双胍缓释(SR)25/500mg片剂或与1片吉格列汀50mg和2片二甲双胍缓释(XR)500mg的松散组合,洗脱7天。连续收集血样直至48小时以测定药物浓度和二肽基肽酶4(DPP-4)活性。在禁食和进食状态下，FDC和松散组合之间吉格列汀和二甲双胍的浓度-时间曲线相似。在两种状态下，FDC与松散组合的浓度-时间曲线下面积以及吉格列汀和二甲双胍的最大血浆浓度的几何平均比率和90％置信区间均在生物等效性范围内（0.8-1.25）。FDC的DPP-4活性-时间曲线与松散组合相当，FDC和松散组合之间的DPP-4抑制时间曲线和最大DPP-4抑制下的面积相似，无论禁食或进食状态。总之,在FDC片剂和松散组合中，吉格列汀和二甲双胍的PK/PD特征在禁食和进食状态下相似。
背景：ClinicalTrials.gov标识符：NCT03355014。
背景：ClinicalTrials.gov标识符：NCT03355014。
