Omarigliptin for the treatment of type 2 diabetes

Tan, Xueying

doi:10.1007/s12020-016-1011-9

Cited by 18 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gliptins are considered to be effective agents for the treatment of type 2 Diabetes Mellitus. Omariglitpin (OTN), Figure 1 , is a long-acting once weekly administered antidiabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor [ 5 , 6 , 7 ]. It has been licensed for use in Japan since 2015 but its phase III development in US has been halted for undisclosed commercial reasons [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

et al. 2020

View full text Add to dashboard Cite

Enhancing drug extraction from human plasma is a challenging approach that critically affects pharmacokinetic and any further clinical studies based on the drug Cmin and Cmax values. It also has a serious impact on the sensitivity and the lower limit of quantification (LLOQ) value of the bio-analytical methods. An advanced liquid chromatography tandem mass spectrometry (LC-MS/MS) bio-analytical method of omarigliptin (25–1000 nM) was established in human plasma using one-step liquid-liquid extraction. Alogliptin was used as an internal standard (IS) to attain good recovery and reproducibility while reducing the effects of the matrix. Enhanced plasma extraction of omarigliptin was successfully achieved with tertiary butyl methyl ether—diethyl ether (TBME-DEE) mixture as the extracting solvent, while using acetonitrile as the diluent solvent for the IS to effectively decrease the formed emulsion. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 399.2 to 153.0 for omarigliptin and m/z 340.2 to 116.0 for alogliptin was employed in positive Electro Spray Ionization (ESI) mode. Human plasma samples were collected after 1.5 h (tmax) of Marizev® (12.5 mg) tablets administration to healthy human volunteers showing average concentration of 292.18 nM. Validation results were all satisfactory including successful stability studies with bias below 12%. The proposed study will be valuable for ethnicity comparison studies that will be commenced on omarigliptin in Egypt by the authors in prospective study, following the FDA recommends, to evaluate possible sub-group dissimilarities that include pharmacokinetic parameters.

show abstract

Section: Introductionmentioning

confidence: 99%

Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

et al. 2020

View full text Add to dashboard Cite

show abstract

“…These include the dipeptidyl peptidase‐4 (DPP‐4) inhibitors, of which Omarigliptin (OMG) is a once weekly version . In contrast to the once‐daily DPP‐4 inhibitors, once‐weekly OMG can improve patients’ adherence and thus achieve optimal therapeutic efficacy . OMG inhibits DPP‐4 to increase incretin levels (GLP‐1 and GIP) which inhibit glucagon release leading to increase in the insulin secretion and decrease in blood glucose levels with added benefits over currently commercially available DPP‐4 inhibitors with excellent pharmacokinetic profile amenable for once‐weekly human dosing .…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the once‐daily DPP‐4 inhibitors, once‐weekly OMG can improve patients’ adherence and thus achieve optimal therapeutic efficacy . OMG inhibits DPP‐4 to increase incretin levels (GLP‐1 and GIP) which inhibit glucagon release leading to increase in the insulin secretion and decrease in blood glucose levels with added benefits over currently commercially available DPP‐4 inhibitors with excellent pharmacokinetic profile amenable for once‐weekly human dosing . OMG (Figure ), is a small‐molecule developed by Merck in Japan and it was generally well‐tolerated with a low incidence of symptomatic hypoglycemia …”

Section: Introductionmentioning

confidence: 99%

Factorial design optimization of micelle enhanced synchronous spectrofluorimetric assay of Omarigliptin: Applied to content uniformity testing and in vitro drug release

2018

View full text Add to dashboard Cite

A micelle enhanced spectrofluorimetric method was developed for determination of Omarigliptin (OMG) based on its native fluorescence behavior. The interaction of OMG with surfactants and macromolecules was studied. In aqueous solution, the relative fluorescence intensity (RFI) of OMG was enhanced by 24% in the presence of Tween 80 at pH 3.5. The optimal conditions for the micelle enhanced fluorescence were attained by Minitab® program using Plackett-Burman factorial design. Pareto chart, contour plots and surface plots were used to exclude the insignificant variables and optimize the significant factors. The spectrofluorimeter was operated under synchronous mode using ∆λ = 30 nm and recording the RFI of the intense narrow band at 267 nm for OMG in 0.5% w/v Tween 80 + 0.2 M acetate buffer (pH 3.5) system using water as diluent. Using synchronous scan mode offered many advantages including considerable reduction of spectral overlap and enhanced linearity of the calibrators. Validation parameters were satisfied over the concentration range 0.1-2 μg/ml. The developed method was the first analytical procedure for OMG assay in Marizev® tablets. Moreover, content uniformity testing and in vitro drug release of tablets were performed.

show abstract

“…It was approved in Japan in 2015 and phase Ⅲ clinical trial had completed (Chen et al, 2015a). Compared to once-daily DPP-4 inhibitor (sitagliptin, linagliptin, vildagliptin, saxagliptin and alogliptin), omarigliptin is more potent to inhibit DPP-4 enzyme (Tan, 2016). Previous study of pharmacokinetics and pharmacodynamics in health subject showed that omarigliptin was supportive of a sustained and clinically meaningful effect; it enhanced medication persistence and adherence of patients, optimized glycemic control and also reduced the risk of complications (Krishna et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Abbreviations used: DPP-4, dipeptidyl peptidase-4; ESI, electrospray ionization; IS, internal standard; LC-MS/MS, liquid chromatography-tandem mass spectrometry; LLOQ, lower limit of quantification; QC, quality control; RE, relative error; RSD, relative standard deviation; T2DM, type 2 diabetes; UHPLC, ultra-high pressure liquid chromatography enzyme (Tan, 2016). A previous study of pharmacokinetics and pharmacodynamics in healthy subjects showed that omarigliptin was supportive of a sustained and clinically meaningful effect; it enhanced medication persistence and adherence of patients, optimized glycemic control and reduced the risk of complications (Krishna et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Ultra‐high pressure liquid chromatography–tandem mass spectrometry method for the determination of omarigliptin in rat plasma and its application to a pharmacokinetic study in rats

2017

Biomedical Chromatography

View full text Add to dashboard Cite

Omarigliptin is a novel long-acting dipeptidyl peptidase-4 inhibitor used for the treatment of type 2 diabetes. In this work, a sensitive and selective ultra-high pressure liquid chromatography tandem mass spectrometry method was developed and validated for the determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on an RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 μm), using gradient mobile phase (0.1% formic acid-acetonitrile) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode, with target fragment ions m/z 399.1 → 152.9 for omarigliptin and m/z 237.1 → 194 for the internal standard. The total run time was 4 min. Retention time of omarigliptin and internal standard was 1.25 and 2.12 min, respectively. Relative standard deviation (%) of the intra- and inter-day precision was below 10.0%, and accuracy was between 97.9% and 105.3%. Calibration curve was established over the range 2-5000 ng/mL with good linearity. The lower limit of quantification and limit of detection of omarigliptin were 2 and 0.25 ng/mL, respectively. Mean recoveries were in the range 87.3-95.1% for omarigliptin. No matrix effect was observed in this method. This novel method has been successfully applied to a pharmacokinetic study of omarigliptin in rats. The absolute bioavailability of omarigliptin was identified as high as 87.31%.

show abstract

Omarigliptin for the treatment of type 2 diabetes

Cited by 18 publications

References 28 publications

Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

Enhanced Extraction Technique of Omarigliptin from Human Plasma—Applied to Biological Samples from Healthy Human Volunteers

Factorial design optimization of micelle enhanced synchronous spectrofluorimetric assay of Omarigliptin: Applied to content uniformity testing and in vitro drug release

Ultra‐high pressure liquid chromatography–tandem mass spectrometry method for the determination of omarigliptin in rat plasma and its application to a pharmacokinetic study in rats

Contact Info

Product

Resources

About