Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H19N3O3S |
Molecular Weight | 357.427 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C3=CC=CC=N3
InChI
InChIKey=YASAKCUCGLMORW-UHFFFAOYSA-N
InChI=1S/C18H19N3O3S/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)
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 |
---|---|---|
Rosiglitazone (BRL49653), a PPARgamma-selective agonist, causes peroxisome proliferator-like liver effects in obese mice. | 1999 Jul |
|
Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells. | 1999 Jun |
|
Troglitazone inhibits mitogenic signaling by insulin in vascular smooth muscle cells. | 2000 May |
|
Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation. | 2002 Apr |
|
Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes. | 2002 Jan |
|
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. | 2002 Jan 11 |
|
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size. | 2002 Jul |
|
Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction. | 2002 May |
|
Rosiglitazone-induced granulomatous hepatitis. | 2002 May-Jun |
|
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. | 2003 Apr |
|
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 |
|
Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al. | 2003 Jan |
|
Rosiglitazone and retinoic acid induce uncoupling protein-1 (UCP-1) in a p38 mitogen-activated protein kinase-dependent manner in fetal primary brown adipocytes. | 2003 Jan 3 |
|
PPARgamma ligands induce prostaglandin production in vascular smooth muscle cells: indomethacin acts as a peroxisome proliferator-activated receptor-gamma antagonist. | 2003 Oct |
|
[Anti-hypertensive effect of rosiglitazone in non-diabetic essential hypertension]. | 2004 Dec |
|
Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute inflammation. | 2004 Jan 1 |
|
Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin. | 2004 Jul 1 |
|
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 |
|
Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism. | 2004 Nov |
|
Chronic heart failure-related interventions after starting rosiglitazone in patients receiving insulin. | 2004 Oct |
|
Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro. | 2004 Oct |
|
The antidiabetic agent rosiglitazone upregulates SERCA2 and enhances TNF-alpha- and LPS-induced NF-kappaB-dependent transcription and TNF-alpha-induced IL-6 secretion in ventricular myocytes. | 2005 |
|
Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury. | 2005 Feb |
|
The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. | 2005 Jan |
|
Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1. | 2005 Jun |
|
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation. | 2005 Mar |
|
Fatty acids and expression of adipokines. | 2005 May 30 |
|
Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions. | 2005 Oct |
|
Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1. | 2005 Sep |
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
by
admin
on
Edited
Fri Dec 15 16:18:29 GMT 2023
by
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on
Fri Dec 15 16:18:29 GMT 2023
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Record UNII |
05V02F2KDG
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C98241
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N0000011272
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A10BD03
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NBK548114
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N0000180190
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A10BD04
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QA10BG02
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N0000175374
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C1934
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QA10BD04
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A10BG02
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N0000170119
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N0000011272
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QA10BD03
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N0000180186
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N0000170119
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N0000011272
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Rosiglitazone
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PRIMARY | RxNorm |
Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TARGET -> INHIBITOR |
Binding Assay
IC50
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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ENANTIOMER -> RACEMATE | |||
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BINDER->LIGAND |
BINDING
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> INHIBITOR |
SUBSTRATE USED: Bromsulphthalein (BSP)
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT | |||
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ENANTIOMER -> RACEMATE |
Related Record | Type | Details | ||
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METABOLITE INACTIVE -> PARENT |
MINOR
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METABOLITE ACTIVE -> PARENT |
MAJOR
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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