更新于：2024-07-01
Repaglinide
瑞格列奈
更新于：2024-07-01
概要
基本信息
药物类型 小分子化药 |
别名 GlucoNorm、Repaglinide (JAN/USP/INN)、AG-EE-388 (racemate) + [16] |
作用机制 钾离子通道阻滞剂、VGKCs阻滞剂(电压门控性钾通道家族阻滞剂) |
治疗领域 |
在研适应症 |
非在研适应症- |
原研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (1997-12-22), |
最高研发阶段(中国)批准上市 |
特殊审评- |
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结构
分子式C27H36N2O4 |
InChIKeyFAEKWTJYAYMJKF-QHCPKHFHSA-N |
CAS号135062-02-1 |
关联
111
项与 瑞格列奈 相关的临床试验The Effect of Multiple Doses of BI 1569912 on the Single-dose Pharmacokinetics of Repaglinide, Midazolam and Bupropion Following Oral Administration in Healthy Male and Female Subjects (an Open-label, 2-period Fixed-sequence Trial)
A Phase 1, Open-Label, Drug-Drug Interaction Study to Assess the Effect of TAK-279 on the Pharmacokinetics of a Sensitive CYP3A4 Substrate and a Sensitive CYP2C8 Substrate in Healthy Subjects
瑞格列奈片在健康受试者中空腹/餐后单次口服给药、随机、开放、两序列、四周期、完全重复交叉生物等效性试验
100 项与 瑞格列奈 相关的临床结果
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100 项与 瑞格列奈 相关的转化医学
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100 项与 瑞格列奈 相关的专利（医药）
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833
项与 瑞格列奈 相关的文献（医药）2024-03-01Talanta
Parallel artificial liquid membrane extraction coupled with UPLC-ESI-MS/MS method for high-throughput quantitation of repaglinide in diabetic patients
Article
作者: Ahmed, Sameh A ; Alahmadi, Yaser M ; Almaghrabi, Mohammed ; Abdallah, Nehad A
A high-throughput therapeutic monitoring method was developed for repaglinide (RPG) in diabetic patients, combining parallel artificial liquid membrane extraction (PALME) with ultraperformance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). PALME was performed using a 96-well donor plate comprising a donor solution containing a plasma sample, 50 mM phosphate buffer (pH = 8.0), and cetirizine (CTZ) as internal standard. A polypropylene (PP) porous membrane served as a selective support for the liquid membrane (SLM), preventing nonspecific binding produced by other membranes. The extraction was accomplished across SLM made of PP membrane with dodecyl acetate and 1 % trioctylamine (w/w), and the acceptor solution comprised DMSO and 200 mM formic acid (50:50, v/v). The simple workflow for PALME provided analyte enrichment, highly efficient sample cleanup, high throughput analysis, and excellent reproducibility. Method validation met FDA criteria, with a linear plasma calibration range (0.1-100 ng mL-1, r = 0.9995) and a lower limit of quantitation (LLOQ) of 0.1 ng mL-1. Recovery results at 98.9 % affirmed method reliability. The ability to analyze 198 samples per hour, coupled with a reduced amount of solvents, underscores the method's high throughput and eco-friendly profile. The PALME-UPLC-ESI-MS/MS method was successfully applied to therapeutic drug monitoring of RPG in diabetic patients following 2 mg RPG tablet administration, establishing its effectiveness.
2024-01-01Methods in molecular biology (Clifton, N.J.)
Analysis of Hypoglycemic Drugs by Liquid Chromatography-Tandem Mass Spectrometry
Article
作者: Langman, Loralie J ; Jannetto, Paul J
A rapid and simple method to measure oral hypoglycemic agents is essential in the evaluation of a patient with spontaneous hypoglycemia. As a result, a robust high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the qualitative detection of first-generation sulfonylureas (e.g., chlorpropamide, tolazamide, and tolbutamide), second-generation sulfonylureas (e.g., glimepiride, glipizide, and glyburide), meglitinides (e.g., repaglinide, nateglinide), and thiazolidinediones (e.g., rosiglitazone and pioglitazone). HPLC involved a C8 column and MS/MS was used in electrospray ionization (ESI) positive mode. Identification of all compounds was made using various multiple-reaction monitoring (MRMs). Isotopic labeled chlorpropamide-d4, glimepiride-d5, glyburide-d11, nateglinide-d5, repaglinide-ethyl-d5, rosiglitazone-d3, and zomepirac were used as the internal standards. The cutoffs for each drug were as follows: chlorpropamide 100 ng/mL, tolazamide 50 ng/mL, tolbutamide 20 ng/mL, glimepiride 20 ng/mL, glipizide 5 ng/mL, glyburide 5 ng/mL, repaglinide 5 ng/mL, rosiglitazone 20 ng/mL, pioglitazone 20 ng/mL, and nateglinide 5 ng/mL.
2024-01-01Clinical pharmacokinetics
Interplay of UDP-Glucuronosyltransferase and CYP2C8 for CYP2C8 Mediated Drug Oxidation and Its Impact on Drug–Drug Interaction Produced by Standardized CYP2C8 Inhibitors, Clopidogrel and Gemfibrozil
Article
作者: Iga, Katsumi ; Kiriyama, Akiko
BACKGROUND AND OBJECTIVE:
Early investigations into drug-drug interactions (DDIs) involving cytochrome P450 2C8 (CYP2C8) have highlighted the complexity of interactions between CYP2C8 substrate drugs, including montelukast, desloratadine, pioglitazone, repaglinide, and cerivastatin (the latter two being OATP1B1 substrates), and standardized CYP2C8 inhibitors such as clopidogrel (Clop) and gemfibrozil (Gem). These interactions have proven challenging to predict based solely on simple CYP inhibition. A hypothesis has emerged suggesting that these substrate drugs first distribute to UDP-glucuronosyltransferase (UGT) before undergoing oxidation by CYP2C8, resulting in bidirectional elimination. The process of drug distribution to UGT is believed to significantly impact these DDIs. This study aims to explore the intricate interplay between UGT and CYP2C8 in the context of DDIs involving CYP2C8 substrates affected by Clop and Gem.
METHODS:
Plasma-level data for the unchanged drug and its metabolite, drawn from the respective literature, formed the basis of our analysis. We evaluated the enzymatic inhibitory activities of DDIs and utilized simulations to estimate plasma levels of the unchanged victim drug and its metabolite in each DDI. This was accomplished by employing a functional relationship that considered the fractional contributions of CYP2C8 and UGT to clearance, perpetrator-specific inhibitory activities against CYP2C8, and drug distribution to UGT.
RESULTS:
Our findings emphasize the pivotal role of UGT-mediated distribution in the context of CYP2C8 substrate metabolism, particularly in the complex DDIs induced by Clop and Gem. In these DDIs, Gem exerts inhibitory effects on both UGT and CYP2C8, whereas Clop (specifically its metabolite, Clop-COOH) solely targets CYP2C8. Importantly, the inhibition of CYP2C8 by both Clop and Gem is achieved through a non-competitive mechanism, driven by the actions of their acyl-glucuronides. Clop and Gem exhibit inhibition activities accounting for 85% (pAi,CYP2C8 = 7) and 93% (pAi,CYP2C8 = 15), respectively. In contrast, Gem's inhibition of UGT is relatively modest (50%, pAi,UGT(d) = 2), and it operates through a non-specific, competitive process in drug distribution to UGT. Within this context, our UGT-CYP2C8 interplay model offers an accurate means of predicting the alterations resulting from DDIs, encompassing changes in plasma levels of the unchanged drug and its metabolites, as well as shifts in metabolite formation rates. Our analysis highlights the critical importance of considering the fractional contributions of CYP2C8 and UGT to the victim drug's clearance (fm,CYP2C8; fm,UGT) in DDI prediction. Furthermore, our examination of DDIs involving OATP1B1 substrate drugs underscores that accounting for the hepatic uptake transporters' role in the liver is superfluous in DDI prediction.
CONCLUSION:
These findings substantially enhance our comprehension of CYP2C8-mediated oxidation and DDIs, holding crucial implications for drug development and the planning of clinical trials involving these inhibitors.
100 项与 瑞格列奈 相关的药物交易
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研发状态
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 2型糖尿病 | 美国 | 1997-12-22 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
N/A | - | 鹹襯觸淵憲鬱餘願糧鹽(襯遞積膚顧餘簾壓蓋衊) = 鬱淵廠糧憲衊獵顧壓繭 艱鏇鑰膚積鹹襯鏇壓廠 (廠窪製願衊簾淵壓齋範 ) | 积极 | 2020-09-23 | |||
Sublingual Repaglinide 1mg + Oral Glucose 75g | 鹹襯觸淵憲鬱餘願糧鹽(襯遞積膚顧餘簾壓蓋衊) = 鑰繭蓋網膚獵艱壓構簾 艱鏇鑰膚積鹹襯鏇壓廠 (廠窪製願衊簾淵壓齋範 ) | ||||||
N/A | 31 | placebo (1 Placebo) | 觸觸願構憲繭鹹簾繭選(鏇蓋憲鹽構鹽願淵範淵) = 膚網鑰鏇鏇齋齋壓鬱願 構壓醖艱遞餘壓鬱淵網 (鑰遞獵餘淵構範膚醖願, 選齋觸鹽鬱衊鹽顧窪網 ~ 範憲齋艱鏇餘鏇醖襯簾) 更多 | - | 2017-06-05 | ||
(2. Repaglinide) | 觸觸願構憲繭鹹簾繭選(鏇蓋憲鹽構鹽願淵範淵) = 餘積獵積網簾齋糧鑰願 構壓醖艱遞餘壓鬱淵網 (鑰遞獵餘淵構範膚醖願, 衊鑰簾糧簾遞選製壓壓 ~ 鬱網鹹窪選艱築製糧積) 更多 | ||||||
临床4期 | 5,570 | (Phase 2: Metformin + Sitagliptin + Glimepiride) | 繭艱範鹽積壓範獵積餘(餘憲憲構蓋鏇襯製鹹衊) = 範餘夢網餘製鹽夢顧網 網衊構餘築積觸餘衊壓 (遞壓夢顧選網糧願齋衊, 餘鹹簾築鏇觸壓鬱鹽醖 ~ 鏇齋廠壓廠憲鹹糧願選) 更多 | - | 2016-05-11 | ||
Repaglinide+Sitagliptin+Metformin (Phase 2: Metformin + Sitagliptin + Repaglinide) | 繭艱範鹽積壓範獵積餘(餘憲憲構蓋鏇襯製鹹衊) = 憲蓋憲淵製廠觸繭窪艱 網衊構餘築積觸餘衊壓 (遞壓夢顧選網糧願齋衊, 願鹹窪壓選網積積鏇糧 ~ 衊鬱壓積艱糧壓願糧襯) 更多 | ||||||
N/A | 2型糖尿病 追加 | - | 艱觸齋築顧憲窪築選簾(願鏇構窪夢壓鬱顧鹽選) = 窪顧廠壓壓觸積構選遞 鏇窪壓餘製網壓壓願構 (窪蓋窪選鏇選積觸簾襯, 9633) 更多 | 积极 | 2015-09-15 | ||
Switch to Repaglinide | 艱觸齋築顧憲窪築選簾(願鏇構窪夢壓鬱顧鹽選) = 積壓壓廠繭醖壓鬱壓遞 鏇窪壓餘製網壓壓願構 (窪蓋窪選鏇選積觸簾襯, 12050) 更多 | ||||||
临床4期 | 440 | (Repaglinide) | 憲膚夢鬱夢鹹蓋構顧獵(襯夢願構獵襯繭淵鹽衊) = 艱簾鏇夢餘積選遞艱遞 鬱鹽鹽顧壓鏇鬱淵夢遞 (構鬱鏇齋願鑰構製襯夢, 鹽醖願獵夢醖淵齋鏇鑰 ~ 獵範選壓淵襯積鬱糧網) 更多 | - | 2011-12-29 | ||
(Gliclazide) | 憲膚夢鬱夢鹹蓋構顧獵(襯夢願構獵襯繭淵鹽衊) = 觸廠鹹簾憲鬱鏇鬱範憲 鬱鹽鹽顧壓鏇鬱淵夢遞 (構鬱鏇齋願鑰構製襯夢, 鑰顧觸鹽蓋獵蓋顧鹽鹹 ~ 夢獵膚襯遞淵齋網餘憲) 更多 | ||||||
临床4期 | 433 | (Repaglinide + Metformin) | 積構選積選餘廠顧鑰鏇(衊廠製糧襯醖窪糧壓構) = 遞選壓網選淵襯淵餘觸 艱窪鑰範艱繭構襯顧觸 (醖憲選齋廠選齋廠遞衊, 蓋淵網窪製憲鬱鹽築鏇 ~ 齋鹹鏇艱製網願繭艱夢) 更多 | - | 2010-12-08 | ||
(Repaglinide) | 積構選積選餘廠顧鑰鏇(衊廠製糧襯醖窪糧壓構) = 糧齋夢獵餘餘顧繭鑰衊 艱窪鑰範艱繭構襯顧觸 (醖憲選齋廠選齋廠遞衊, 積鹽構觸廠選蓋構觸觸 ~ 壓網鹽糧構積願構築衊) 更多 |
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