ROSIGLITAZONE FUMARATE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H19N3O3S.C4H4O4
Molecular Weight	473.499
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C\C(O)=O.CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C3=CC=CC=N3

InChI

InChIKey=SUFUKZSWUHZXAV-WLHGVMLRSA-N

InChI=1S/C18H19N3O3S.C4H4O4/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;5-3(6)1-2-4(7)8/h2-9,15H,10-12H2,1H3,(H,20,22,23);1-2H,(H,5,6)(H,7,8)/b;2-1+

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10764590	Agonist 2678		40.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf	Primary		Approved 8429	AVANDIA Approved Use After 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 Date 1999

C_max

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

T_1/2

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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 Page: p.105	DLT: Headache, Malaise... Disc. AE: Pain in leg... Dose limiting toxicities: Headache (3.1%) Malaise (3.1%) Oedema legs (9.4%) AEs leading to discontinuation/dose reduction: Pain in leg (3.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/18503774 Page: p.105
20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25390127 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: https://pubmed.ncbi.nlm.nih.gov/25390127 Page: p.73,74	Disc. AE: Macular edema... AEs leading to discontinuation/dose reduction: Macular edema Sources: https://pubmed.ncbi.nlm.nih.gov/25390127 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	Disc. AE: Congestive heart failure, Myocardial ischemia... AEs leading to discontinuation/dose reduction: Congestive heart failure Myocardial ischemia (2%) Fluid retention Edema Weight gain Anemia Macular edema Fracture bone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1

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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 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: https://pubmed.ncbi.nlm.nih.gov/18503774 Page: p.105
Macular edema	Disc. AE	20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25390127 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: https://pubmed.ncbi.nlm.nih.gov/25390127 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf Page: p.1

PubMed

Title	Date	PubMed
Rosiglitazone (BRL49653), a PPARgamma-selective agonist, causes peroxisome proliferator-like liver effects in obese mice.	1999 Jul	10393202
Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells.	1999 Jun	10364093
Regulation of gene expression by activation of the peroxisome proliferator-activated receptor gamma with rosiglitazone (BRL 49653) in human adipocytes.	1999 Nov	10548525
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	10529360
Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone.	2000 Apr	10871190
A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation.	2000 Jan 21	10636887
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.	2000 Mar	10882139
Troglitazone inhibits mitogenic signaling by insulin in vascular smooth muscle cells.	2000 May	10813377
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	11139385
Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages.	2001 May 4	11343698
Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation.	2002 Apr	11916924
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons.	2002 Jan 11	11750908
Peroxisome proliferator-activated receptor agonists inhibit inflammatory edema and hyperalgesia.	2002 Jun	12083418
Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro.	2002 Jun	12055599
Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction.	2002 May	11978674
Rosiglitazone-induced granulomatous hepatitis.	2002 May-Jun	11960075
Accelerated hypertension due to rosiglitazone therapy.	2002 Nov-Dec	12674195
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition.	2003 Apr	12642470
PPAR gamma-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNF alpha secretion is not mediated by PTEN regulation.	2003 Apr 11	12670479
15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia.	2003 Apr 25	12584205
Expression of phosphoenolpyruvate carboxykinase gene in human adipose tissue: induction by rosiglitazone and genetic analyses of the adipocyte-specific region of the promoter in type 2 diabetes.	2003 Dec	14739078
Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes.	2003 Dec	14671216
Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes.	2003 Dec	14595539
Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al.	2003 Jan	12571610
Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.	2003 Jul	12814394
Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells.	2003 Jul 1	12839938
A phase II trial with rosiglitazone in liposarcoma patients.	2003 Oct 20	14562008
Cinnamic acid based thiazolidinediones inhibit human P450c17 and 3beta-hydroxysteroid dehydrogenase and improve insulin sensitivity independent of PPARgamma agonist activity.	2004 Apr	15072549
The PPARgamma ligands PGJ2 and rosiglitazone show a differential ability to inhibit proliferation and to induce apoptosis and differentiation of human glioblastoma cell lines.	2004 Aug	15254749
Decreased expression of peroxisome proliferator activated receptor gamma in cftr-/- mice.	2004 Aug	15174093
[Anti-hypertensive effect of rosiglitazone in non-diabetic essential hypertension].	2004 Dec	15730735
Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin.	2004 Jul 1	15183127
Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy.	2004 Mar 23	14993120
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	15504970
Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism.	2004 Nov	15314095
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation.	2004 Oct 22	15381068
Rosiglitazone, PPAR-gamma receptor ligand, decreases the viability of rat prolactin-secreting pituitary tumor cells in vitro.	2005 Feb	15726020
The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.	2005 Mar	15735429
Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPARgamma-independent mechanism.	2005 Mar	15729575
Development of a complex scintillation proximity assay for high-throughput screening of PPARgamma modulators.	2005 Mar	15715931
Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.	2005 Mar	15715889
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.	2005 Mar	15591153
Effects of metformin and rosiglitazone treatment on insulin signaling and glucose uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled study.	2005 May	15855334
Selective activation of PPARgamma in breast, colon, and lung cancer cell lines.	2005 May 12	15866424

Patents

Sample Use Guides

In Vivo Use Guide

Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily.

Route of Administration: Oral

In Vitro Use Guide

Rosiglitazone treatment (5 uM) prevents NO and prostacyclin overproduction by inhibiting microparticles-induced iNOS and COX-2 expression.

Name

Type

Language

ROSIGLITAZONE FUMARATE

Common Name

English

2,4-THIAZOLIDINEDIONE, 5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-, (2E)-2-BUTENEDIOATE (1:1)

Systematic Name

English

Code System Code Type Description

FDA UNII

533QLZ62ZS

Created by admin on Sat Dec 16 11:38:26 GMT 2023 , Edited by admin on Sat Dec 16 11:38:26 GMT 2023

PRIMARY

CAS

403647-10-9

Created by admin on Sat Dec 16 11:38:26 GMT 2023 , Edited by admin on Sat Dec 16 11:38:26 GMT 2023

PRIMARY

PUBCHEM

6537720

Created by admin on Sat Dec 16 11:38:26 GMT 2023 , Edited by admin on Sat Dec 16 11:38:26 GMT 2023

PRIMARY

ACTIVE MOIETY


					05V02F2KDG

ROSIGLITAZONE

SUBSTANCE RECORD


					533QLZ62ZS

ROSIGLITAZONE FUMARATE

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2