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更新于：2026-10-23
Repaglinide
瑞格列奈
更新于：2026-10-23
概要
基本信息
原研机构 |
权益机构- |
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/序列
分子式C27H36N2O4 |
InChIKeyFAEKWTJYAYMJKF-QHCPKHFHSA-N |
CAS号135062-02-1 |
关联
132
项与 瑞格列奈 相关的临床试验NCT07881224
A Phase 1, Non-randomized, Fixed-sequence, Multiple-dose Study Investigating the Drug-drug Interaction Potential and QTc Effects of Fosmanogepix in Healthy Adult Subjects
NCT07340190
A Phase 1b, Open Label, 2-Part Study to Evaluate the Effect of Pelabresib (DAK539/CPI-0610) on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Drospirenone/Ethinyl Estradiol Oral Contraceptive in Patients With Advanced Malignancies
CTR20261478
瑞格列奈片在中国健康试验参与者中进行的单中心、随机、开放、单次口服给药、两制剂、两序列、两周期、交叉（空腹）/两序列、四周期、完全重复交叉（餐后）的人体生物等效性试验
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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1,401
项与 瑞格列奈 相关的文献（医药）2026-10-01CLINICAL PHARMACOLOGY & THERAPEUTICS
Identification of a Functional
CYP2C8
Variant Allele that Alters Splicing, Reduces Protein Expression, and Increases Drug Exposure
Article
作者: Schwab, Matthias ; Tzvetkov, Mladen ; Tapaninen, Tuija ; Klein, Kathrin ; Backman, Janne T. ; Kiiski, Johanna I. ; Hirvensalo, Päivi ; Niemi, Mikko ; Pihlajamäki, Jussi ; Grube, Markus ; Neuvonen, Mikko ; Männistö, Ville T. ; Kaminska, Dorota ; Mykkänen, Anssi J. H. ; Tornio, Aleksi
This study investigated genetic determinants of the pharmacokinetics of the CYP2C8 index drugs repaglinide and gemfibrozil, and their interaction in healthy participants. Sequencing data from a study with montelukast revealed a novel functional
CYP2C8
allele (rs2071426,
CYP2C8*19
), predicted to create an intronic splice donor site. In human liver samples,
CYP2C8*19
associated with transcript‐specific changes in
CYP2C8
mRNA expression, reduced CYP2C8 protein expression, and decreased enzyme activity. Consistently, participants with the
CYP2C8*19
/
*19
genotype had 45% greater area under the plasma repaglinide concentration–time curve from time zero to infinity (AUC
0‐∞
) than participants with
CYP2C8*1
/
*1
(
P
= 1.6 × 10
−4
). Participants with
CYP2C8*1
/
*3
had 26% smaller AUC
0‐∞
(
P
= 0.0033) and those with
CYP2C8*1
/
*4
had 51% greater AUC
0‐∞
(
P
= 8.2 × 10
−4
). The fold increase in repaglinide AUC
0‐∞
caused by gemfibrozil was 36% (
P
= 1.3 × 10
−4
) smaller in
CYP2C8*19
/
*19
participants than in
CYP2C8*1
/
*1
participants. In a genome‐wide association study (GWAS),
SLCO1B1
c.521 T>C (rs4149056) associated with increased repaglinide AUC
0‐∞
(
P
= 4.5 × 10
−15
;
n
= 172) and
SLCO1A2
variants associated with decreased AUC
0‐∞
(
P
< 10
−8
). In a GWAS of repaglinide after gemfibrozil pretreatment,
SLCO1C1
variants associated with decreased AUC
0‐∞
(
P
< 1.6 × 10
−8
;
n
= 66). Participants with the poor function
SLCO1B1
genotype showed a 32% smaller fold increase in repaglinide AUC
0‐∞
following gemfibrozil than participants with the normal function
SLCO1B1
genotype (
P
= 0.0045). This study characterizes
CYP2C8*19
as a novel decreased function allele and shows that
CYP2C8
and
SLCO1B1
genotypes affect the gemfibrozil–repaglinide interaction.
2026-10-01DRUG METABOLISM AND DISPOSITION
Repaglinide metabolism by human hepatocytes reveals CYP2C8 dominance and misassignment of CYP3A4 by liver subcellular fractions and recombinant enzymes
Article
作者: Bapiro, Tashinga E
Repaglinide is an antidiabetic agent and Food and Drug Administration-endorsed clinical CYP2C8 probe with a well characterized human disposition profile in which a dicarboxylic acid, M2, is the main metabolite accounting for 66% of the administered dose. The remainder is distributed among M1 (4%), unchanged repaglinide (2%), M4 (<0.5%), several minor metabolites (each <1%), and some unidentified metabolites. Although substantial in vivo evidence supports repaglinide as a CYP2C8 probe, in vitro studies indicate a greater CYP3A4 contribution to its overall metabolism. Previous research using chemical inhibitors in human liver subcellular fractions and recombinant enzymes consistently assigned M1 and M4 formation to CYP3A4 and CYP2C8, respectively, with M2 predominantly formed via a CYP3A4-mediated first-step and subsequent completion by a cytosolic enzyme. However, corresponding experiments using chemical inhibitors were not conducted in human hepatocytes (HH). Motivated by our recent data indicating potential misassignment of CYP3A4 involvement by human liver microsomes and recombinant enzymes, this study compared these matrices with HH. Here, human liver microsomes, liver S9, and recombinant enzymes also assigned M1 and M4 formation to CYP3A4 and CYP2C8, respectively. In contrast, slightly over half of M1 formed in HH was attributed to CYP2C8, a surprising result given the enzyme's lower hepatic expression and minimal contribution in subcellular fractions. M4 formation remained predominantly CYP2C8-dependent in HH. Crucially, and contrary to results in subcellular fractions, HH showed minimal CYP3A4 involvement in the formation of the major in vivo metabolite M2, firmly establishing CYP2C8 as the primary enzyme. These findings provide robust data for rationalizing repaglinide pharmacokinetics and demonstrate a real risk of CYP3A4 misassignment when relying solely on liver subcellular fractions or recombinant enzymes. SIGNIFICANCE STATEMENT: The author and colleagues recently discovered that human liver microsomes and recombinant enzymes can misidentify CYP3A4 as the main savolitinib-metabolizing enzyme. It is, therefore, crucial for researchers and regulatory authorities to understand the risk of misassignment. This study shows that the same phenomenon underlies the inconsistent in vitro-in vivo relative contributions of CYP3A4 and CYP2C8 to repaglinide metabolism that have been difficult to explain and demonstrates that liver subcellular fractions and recombinant enzymes pose a real risk for enzyme misidentification.
2026-09-01JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Ultrafast affinity extraction with non-covalent entrapment for biointeraction analysis: development and applications to single- and multi-site drug-protein binding
Article
作者: Kyei, Isaac ; Pinky, Nigar Sultana ; Suh, Kyungah ; Gonzales, Moira ; Hage, Benjamin D ; Hage, David S
Reversible biomolecular interactions play a vital role in numerous biological processes. One of the techniques that has been developed to evaluate solution-phase binding and rate constants for such processes is ultrafast affinity extraction (UAE). In UAE, a microcolumn containing an immobilized capture agent is used to quickly remove the free form of a target solute from a sample that also contains a soluble binding agent. This separation is typically done on the millisecond-to-second time scale. The measured level of the captured fraction can then be utilized to estimate the binding and rate constants for the interactions between the solute and binding agent in the sample. Covalent coupling methods have been used in the past with UAE to immobilize serum proteins as capture agents for various drugs. This work examines the combination of non-covalent entrapment to immobilize human serum albumin (HSA) as a capture agent within microcolumns that are then used in UAE to study drug interactions with soluble HSA. This combined approach is evaluated using racemic warfarin and repaglinide as model drugs with known single-site or multi-site binding to this protein. The theoretical and experimental behavior of UAE is examined in each case. The binding and rate constants determined by this method are also compared to reference values, including results obtained by UAE using a covalently immobilized capture agent. The results are then used to identify the potential strengths or limitations of this approach and to provide guidelines on how this method can be applied in the future to examine other types of biointeractions.
100 项与 瑞格列奈 相关的药物交易
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研发状态
批准上市
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 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 囊性纤维化 | 临床3期 | 美国 | 2001-06-01 | |
| 囊性纤维化 | 临床3期 | 加拿大 | 2001-06-01 | |
| 糖尿病 | 临床3期 | 美国 | 2001-06-01 | |
| 糖尿病 | 临床3期 | 加拿大 | 2001-06-01 | |
| 高血糖 | 临床2期 | 加拿大 | 2003-11-01 | |
| 囊性纤维化相关糖尿病 | 临床阶段不明 | 美国 | 2006-11-01 | |
| 胰腺外分泌功能不全 | 临床阶段不明 | 美国 | 2006-11-01 | |
| 糖尿病前期 | 临床阶段不明 | 美国 | 2006-11-01 |
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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 | 31 | placebo (1 Placebo) | 廠餘壓淵膚遞襯醖夢膚(鑰夢衊襯獵艱膚觸鹽網) = 獵獵廠鬱網餘餘襯選憲 窪觸壓糧鹽艱積憲範憲 (夢膚夢範構網醖蓋鏇遞, 願選膚範衊壓獵簾遞鬱 ~ 夢構構鹽憲齋糧餘積製) 更多 | - | 2017-06-05 | ||
(2. Repaglinide) | 廠餘壓淵膚遞襯醖夢膚(鑰夢衊襯獵艱膚觸鹽網) = 艱鹹製淵夢膚夢製構糧 窪觸壓糧鹽艱積憲範憲 (夢膚夢範構網醖蓋鏇遞, 願獵觸鬱襯繭範觸繭廠 ~ 壓鑰衊繭顧獵鏇鑰觸壓) 更多 | ||||||
临床4期 | 5,570 | (Phase 2: Metformin + Sitagliptin + Glimepiride) | 網廠製鑰齋鏇觸糧窪廠(淵衊憲醖選鬱範簾壓艱) = 淵廠壓膚廠鏇鑰鹹鬱積 積鏇餘遞鑰繭繭夢壓襯 (構鹹糧製糧艱網願襯壓, 鬱鹽觸淵鹽鹹鹹鏇選夢 ~ 窪選製簾鑰蓋襯製鹹製) 更多 | - | 2016-05-11 | ||
(Phase 2: Metformin + Sitagliptin + Repaglinide) | 網廠製鑰齋鏇觸糧窪廠(淵衊憲醖選鬱範簾壓艱) = 顧鏇糧艱醖簾積範觸製 積鏇餘遞鑰繭繭夢壓襯 (構鹹糧製糧艱網願襯壓, 製膚獵餘簾膚築網壓醖 ~ 廠醖積範鹽願選蓋鹽衊) 更多 | ||||||
临床4期 | 440 | (Repaglinide) | 糧廠簾鬱鹽夢餘襯鹹糧(齋窪鬱積顧製鏇構鏇齋) = 餘餘構簾製製壓衊願鑰 廠積醖鬱鹹衊齋淵顧餘 (蓋齋醖鹽膚廠襯鑰鏇鹽, 0.051) 更多 | - | 2011-12-29 | ||
(Gliclazide) | 糧廠簾鬱鹽夢餘襯鹹糧(齋窪鬱積顧製鏇構鏇齋) = 膚廠製蓋繭顧淵夢鹹繭 廠積醖鬱鹹衊齋淵顧餘 (蓋齋醖鹽膚廠襯鑰鏇鹽, 0.051) 更多 | ||||||
临床4期 | 433 | (Repaglinide + Metformin) | 選艱製範艱願繭鏇窪獵(夢艱窪糧醖願觸築壓齋) = 鹽壓願選鏇醖觸憲繭鬱 廠網繭壓襯網製衊糧鹽 (顧窪憲觸艱襯衊顧鹽鹽, 0.070) 更多 | - | 2010-12-08 | ||
(Repaglinide) | 選艱製範艱願繭鏇窪獵(夢艱窪糧醖願觸築壓齋) = 鏇鑰簾鏇鑰構選遞願艱 廠網繭壓襯網製衊糧鹽 (顧窪憲觸艱襯衊顧鹽鹽, 0.071) 更多 | ||||||
临床4期 | 459 | Insulin plus metformin | 廠獵糧構選糧淵蓋選鏇(顧廠顧糧選鑰夢製簾構) = 簾窪襯觸獵艱鏇衊鹹網 網鬱簾憲繭艱遞繭顧襯 (製窪淵艱齋蓋範範窪鑰, (1.32)) | - | 2009-11-09 | ||
Insulin plus repaglinide | 廠獵糧構選糧淵蓋選鏇(顧廠顧糧選鑰夢製簾構) = 廠觸醖構鹹廠鹽夢製淵 網鬱簾憲繭艱遞繭顧襯 (製窪淵艱齋蓋範範窪鑰, (0.66)) |
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