Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H18N3O3S.K |
Molecular Weight | 395.517 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[K+].CN(CCOC1=CC=C(CC2SC(=O)[N-]C2=O)C=C1)C3=CC=CC=N3
InChI
InChIKey=RWOGCLSZSSKLEN-UHFFFAOYSA-M
InChI=1S/C18H19N3O3S.K/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15;/h2-9,15H,10-12H2,1H3,(H,20,22,23);/q;+1/p-1
Molecular Formula | K |
Molecular Weight | 39.0983 |
Charge | 1 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C18H19N3O3S |
Molecular Weight | 357.427 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionCurator's Comment: description was created based on several sources, including:
https://www.drugs.com/mtm/rosiglitazone.html
http://www.rxlist.com/avandia-drug.htm
http://www.wikidoc.org/index.php/Rosiglitazone
Curator's Comment: description was created based on several sources, including:
https://www.drugs.com/mtm/rosiglitazone.html
http://www.rxlist.com/avandia-drug.htm
http://www.wikidoc.org/index.php/Rosiglitazone
Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. It is FDA approved for the treatment of as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Inhibitors of CYP2C8 (e.g., gemfibrozil) may increase rosiglitazone levels; inducers of CYP2C8 (e.g., rifampin) may decrease rosiglitazone levels. Common adverse reactions include edema, weight gain, and headache.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
40.0 nM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | AVANDIA Approved UseAfter consultation with a healthcare professional who has considered and advised the patient of the risks and benefits of rosiglitazone, AVANDAMET® is indicated as an adjunct to diet and exercise to improve glycemic control when treatment with both rosiglitazone and metformin is appropriate in adults with type 2 diabetes mellitus who either are: already taking rosiglitazone, or not already taking rosiglitazone and unable to achieve glycemic control on other diabetes medications and, in consultation with their healthcare provider, have decided not to take pioglitazone (ACTOS®) or pioglitazone-containing products (ACTOPLUS MET®, ACTOPLUS MET XR®, DUETACT®) for medical reasons. Other Important Limitations of Use: Due to its mechanism of action, rosiglitazone is active only in the presence of endogenous insulin. Therefore, AVANDAMET should not be used in patients with type 1 diabetes. Coadministration of AVANDAMET with insulin is not recommended [see Warnings and Precautions (5.2, 5.3) Launch Date1999 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
432 ng/mL DRUG LABEL https://www.fda.gov/media/75754/download |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
ROSIGLITAZONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: FED |
|
598 ng/mL DRUG LABEL https://www.fda.gov/media/75754/download |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
ROSIGLITAZONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2890 ng × h/mL DRUG LABEL https://www.fda.gov/media/75754/download |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
ROSIGLITAZONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: FED |
|
2971 ng × h/mL DRUG LABEL https://www.fda.gov/media/75754/download |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
ROSIGLITAZONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.59 h DRUG LABEL https://www.fda.gov/media/75754/download |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
ROSIGLITAZONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: FED |
|
3.37 h DRUG LABEL https://www.fda.gov/media/75754/download |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
ROSIGLITAZONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.105 |
unhealthy, 53.1 n = 32 Health Status: unhealthy Condition: Nonalcoholic steatohepatitis Age Group: 53.1 Sex: M+F Population Size: 32 Sources: Page: p.105 |
DLT: Headache, Malaise... Disc. AE: Pain in leg... Dose limiting toxicities: Headache (3.1%) AEs leading toMalaise (3.1%) Oedema legs (9.4%) discontinuation/dose reduction: Pain in leg (3.1%) Sources: Page: p.105 |
20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.73,74 |
unhealthy, 60 n = 1 Health Status: unhealthy Condition: Type 2 diabetes mellitus Age Group: 60 Sex: M Population Size: 1 Sources: Page: p.73,74 |
Disc. AE: Macular edema... AEs leading to discontinuation/dose reduction: Macular edema Sources: Page: p.73,74 |
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Disc. AE: Congestive heart failure, Myocardial ischemia... AEs leading to discontinuation/dose reduction: Congestive heart failure Sources: Page: p.1Myocardial ischemia (2%) Fluid retention Edema Weight gain Anemia Macular edema Fracture bone |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Headache | 3.1% DLT |
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.105 |
unhealthy, 53.1 n = 32 Health Status: unhealthy Condition: Nonalcoholic steatohepatitis Age Group: 53.1 Sex: M+F Population Size: 32 Sources: Page: p.105 |
Malaise | 3.1% DLT |
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.105 |
unhealthy, 53.1 n = 32 Health Status: unhealthy Condition: Nonalcoholic steatohepatitis Age Group: 53.1 Sex: M+F Population Size: 32 Sources: Page: p.105 |
Pain in leg | 3.1% Disc. AE |
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.105 |
unhealthy, 53.1 n = 32 Health Status: unhealthy Condition: Nonalcoholic steatohepatitis Age Group: 53.1 Sex: M+F Population Size: 32 Sources: Page: p.105 |
Oedema legs | 9.4% DLT |
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.105 |
unhealthy, 53.1 n = 32 Health Status: unhealthy Condition: Nonalcoholic steatohepatitis Age Group: 53.1 Sex: M+F Population Size: 32 Sources: Page: p.105 |
Macular edema | Disc. AE | 20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: Page: p.73,74 |
unhealthy, 60 n = 1 Health Status: unhealthy Condition: Type 2 diabetes mellitus Age Group: 60 Sex: M Population Size: 1 Sources: Page: p.73,74 |
Myocardial ischemia | 2% Disc. AE |
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Anemia | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Congestive heart failure | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Edema | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Fluid retention | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Fracture bone | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Macular edema | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
Weight gain | Disc. AE | 8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: Page: p.1 |
PubMed
Title | Date | PubMed |
---|---|---|
Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. | 1999 Jun |
|
Regulation of gene expression by activation of the peroxisome proliferator-activated receptor gamma with rosiglitazone (BRL 49653) in human adipocytes. | 1999 Nov |
|
PPARalpha activation by Wy 14643 induces transactivation of the rat UCP-1 promoter without increasing UCP-1 mRNA levels and attenuates PPARgamma-mediated increases in UCP-1 mRNA levels induced by rosiglitazone in fetal rat brown adipocytes. | 1999 Oct 22 |
|
v- and t-SNARE protein expression in models of insulin resistance: normalization of glycemia by rosiglitazone treatment corrects overexpression of cellubrevin, vesicle-associated membrane protein-2, and syntaxin 4 in skeletal muscle of Zucker diabetic fatty rats. | 2000 Apr |
|
A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. | 2000 Jan 21 |
|
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors. | 2000 Mar |
|
Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. | 2000 May 10 |
|
Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway. | 2001 Feb |
|
Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to alpha and gamma isoforms of peroxisome-proliferator-activated receptors by competing with agonists. | 2001 Jan 15 |
|
Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes. | 2001 May |
|
Peroxisome proliferator-activated receptor agonists inhibit inflammatory edema and hyperalgesia. | 2002 Jun |
|
Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. | 2002 Jun |
|
Peroxisome proliferator-activated receptor-gamma represses GLUT4 promoter activity in primary adipocytes, and rosiglitazone alleviates this effect. | 2003 Aug 15 |
|
Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes. | 2003 Dec |
|
Diminished production of nitric oxide synthase cofactor tetrahydrobiopterin by rosiglitazone in adipocytes. | 2003 Feb 15 |
|
Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells. | 2003 Jul 1 |
|
AhR- and ERK-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-gamma1 expression and subsequent adipocyte differentiation. | 2003 May 15 |
|
Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, ligands of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), reduce ischaemia/reperfusion injury of the gut. | 2003 Sep |
|
Decreased expression of peroxisome proliferator activated receptor gamma in cftr-/- mice. | 2004 Aug |
|
Effect of peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, on dedifferentiated thyroid cancers. | 2004 Dec |
|
A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist. | 2004 Dec 15 |
|
Evidence for a potent antiinflammatory effect of rosiglitazone. | 2004 Jun |
|
Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy. | 2004 Mar 23 |
|
Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-gamma and retinoid X receptor heterodimer. | 2004 May 15 |
|
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. | 2004 Nov |
|
Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone. | 2004 Nov |
|
Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism. | 2004 Nov |
|
Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro. | 2004 Oct |
|
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes. | 2005 Aug |
|
Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury. | 2005 Feb |
|
Chaperone proteins involved in troglitazone-induced toxicity in human hepatoma cell lines. | 2005 Feb |
|
The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. | 2005 Jan |
|
Development of a complex scintillation proximity assay for high-throughput screening of PPARgamma modulators. | 2005 Mar |
|
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. | 2005 Mar |
|
The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes. | 2005 May |
|
Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma. | 2005 May |
|
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway. | 2005 May |
Sample Use Guides
Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18039959
Rosiglitazone treatment (5 uM) prevents NO and prostacyclin overproduction by inhibiting microparticles-induced iNOS and COX-2 expression.
Substance Class |
Chemical
Created
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admin
on
Edited
Sat Dec 16 11:18:22 GMT 2023
by
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Record UNII |
2V3E7D3089
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Record Status |
Validated (UNII)
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Record Version |
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316371-84-3
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