A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.

BACKGROUND: In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. METHODS: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. RESULTS: The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. CONCLUSION: The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

Evaluation of the pharmacokinetics of the DPP-4 inhibitor gemigliptin when coadministered with rosuvastatin or irbesartan to healthy subjects.

OBJECTIVE: Gemigliptin is a selective DPP4 inhibitor used to treat type 2 diabetes. The objective of this study was to evaluate the pharmacokinetics (PKs) of gemigliptin, rosuvastatin, and irbesartan monotherapies and combination therapies. RESEARCH DESIGN AND METHODS: Randomized, open-label, three-treatment, six-sequence, three-period, crossover studies were performed on healthy male volunteers. The three treatments were: 50 mg gemigliptin alone; 20 mg rosuvastatin (part A) or 300 mg irbesartan alone (part B); and rosuvastatin or irbesartan with concomitant gemigliptin. Each drug was administered as part of once daily, 7 day, repeated dosing regimens with a 14 day washout period. CLINICAL TRIAL REGISTRATION: NCT01823133 (part A) and NCT01825850 (part B). MAIN OUTCOME MEASURES: The primary PK parameters - Cmax and AUCτ - were compared to the geometric mean ratios (GMRs) and 90% confidence intervals (90% CIs) that were determined for the combination therapies and monotherapies. RESULTS: A total of 60 participants were administered the study drugs, and 52 participants (27 participants in part A; 25 participants in part B) were analyzed as part of the PK dataset. In part A, the GMRs (gemigliptin + rosuvastatin/gemigliptin) of the Cmax and AUCτ values of gemigliptin were 0.955 (90% CI = 0.874-1.044) and 1.023 (90% CI = 0.991-1.057), and those of rosuvastatin were 1.012 (90% CI = 0.946-1.084) and 1.086 (90% CI = 1.032-1.142), respectively. In part B, the GMRs of the Cmax and AUCτ values of gemigliptin were 1.046 (90% CI = 0.964-1.134) and 1.035 (90% CI = 1.005-1.065), and those of irbesartan were 0.966 (90% CI = 0.897-1.040) and 1.050 (90% CI = 0.993-1.111), respectively. The limitations of this study include its relatively short treatment period and small sample size, as only healthy participants were included. CONCLUSIONS: Gemigliptin does not affect the PK properties of rosuvastatin or irbesartan; also, rosuvastatin and irbesartan do not affect the PKs of gemigliptin.

A quasi-solid-state rechargeable lithium-oxygen battery based on a gel polymer electrolyte with an ionic liquid.

A quasi-solid-state lithium-oxygen battery constructed using a gel polymer electrolyte with an ionic liquid is proposed. The battery architecture incorporates a design feature that can be easily scaled up in size for use in large systems. The feasibility study demonstrates that the battery operates successfully for repeated discharge-charge cycles.

Doped lanthanum nickelates with a layered perovskite structure as bifunctional cathode catalysts for rechargeable metal-air batteries.

Rechargeable metal-air batteries have attracted a great interest in recent years because of their high energy density. The critical challenges facing these technologies include the sluggish kinetics of the oxygen reduction-evolution reactions on a cathode (air electrode). Here, we report doped lanthanum nickelates (La2NiO4) with a layered perovskite structure that serve as efficient bifunctional electrocatalysts for oxygen reduction and evolution in an aqueous alkaline electrolyte. Rechargeable lithium-air and zinc-air batteries assembled with these catalysts exhibit remarkably reduced discharge-charge voltage gaps (improved round-trip efficiency) as well as high stability during cycling.