ROSIGLITAZONE MALEATE

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-BTJKTKAUSA-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
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.	2002 Jul	12087064
Peroxisome proliferator-activated receptor agonists inhibit inflammatory edema and hyperalgesia.	2002 Jun	12083418
AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats.	2002 Nov	12401884
Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone.	2002 Nov	12401879
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
Reduction in the evolution of murine type II collagen-induced arthritis by treatment with rosiglitazone, a ligand of the peroxisome proliferator-activated receptor gamma.	2003 Dec	14674008
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
Diminished production of nitric oxide synthase cofactor tetrahydrobiopterin by rosiglitazone in adipocytes.	2003 Feb 15	12566086
A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs.	2003 Feb 7	12565875
Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al.	2003 Jan	12571610
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
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	12414803
Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.	2003 Jul	12814394
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	12758056
PPARgamma ligands induce prostaglandin production in vascular smooth muscle cells: indomethacin acts as a peroxisome proliferator-activated receptor-gamma antagonist.	2003 Oct	12897060
Induction of apoptosis by mono(2-ethylhexyl)phthalate (MEHP) in U937 cells.	2003 Oct 15	12927354
A phase II trial with rosiglitazone in liposarcoma patients.	2003 Oct 20	14562008
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	12970094
Cinnamic acid based thiazolidinediones inhibit human P450c17 and 3beta-hydroxysteroid dehydrogenase and improve insulin sensitivity independent of PPARgamma agonist activity.	2004 Apr	15072549
Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma2 in the modulation of insulin secretion.	2004 Apr	14625208
Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes.	2004 Aug	15277403
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
[Anti-hypertensive effect of rosiglitazone in non-diabetic essential hypertension].	2004 Dec	15730735
Effect of peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, on dedifferentiated thyroid cancers.	2004 Dec	15640776
Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats.	2004 Dec 1	15526359
A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist.	2004 Dec 15	15556564
Bone is a target for the antidiabetic compound rosiglitazone.	2004 Jan	14500573
Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-gamma, reduces acute inflammation.	2004 Jan 1	14709329
Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin.	2004 Jul 1	15183127
Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis.	2004 Jun 4	15073165
PPAR(gamma) agonist rosiglitazone improves vascular function and lowers blood pressure in hypertensive transgenic mice.	2004 Mar	14744930
Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy.	2004 Mar 23	14993120
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.	2004 May	15089784
Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism.	2004 Nov	15314095
Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors.	2005	15865214
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005 Aug	15860655
Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.	2005 Feb	15684285
Chaperone proteins involved in troglitazone-induced toxicity in human hepatoma cell lines.	2005 Feb	15525695
The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes.	2005 Jan	15619071
Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats.	2005 Jun	15887043
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	15864539
Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism.	2005 Mar	15751073
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.	2005 Mar	15591153
The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes.	2005 May	15855579
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway.	2005 May	15684043
Selective activation of PPARgamma in breast, colon, and lung cancer cell lines.	2005 May 12	15866424
Fatty acids and expression of adipokines.	2005 May 30	15949695
Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions.	2005 Oct	15941851
Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1.	2005 Sep	15908479

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 MALEATE

Official Name

English

ROSIGLITAZONE MALEATE [VANDF]

Common Name

English

ROSIGLITAZONE MALEATE [USP MONOGRAPH]

Common Name

English

ROSIGLITAZONE MALEATE [USP-RS]

Common Name

English

ROSIGLITAZONE MALEATE [MART.]

Common Name

English

BRL-49653-C

Code

English

ROSIGLITAZONE MALEATE [JAN]

Common Name

English

ROSIGLITZAZONE MALEATE

Common Name

English

NSC-717764

Code

English

ROSIGLITAZONE MALEATE [USAN]

Common Name

English

5-((4-(2-(N-METHYL-N-2-PYRIDYLAMINO)ETHOXY)PHENYL)METHYL)THIAZOLIDINE-2,4-DIONE MALEATE

Systematic Name

English

ROSIGLITAZONE MALEATE [MI]

Common Name

English

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

Systematic Name

English

ROSIGLITAZONE MALEATE [ORANGE BOOK]

Common Name

English

(±)-5-(P-(2-(METHYL-2-PYRIDYLAMINO)ETHOXY)BENZYL)-2,4-THIAZOLIDINEDIONE MALEATE (1:1)

Common Name

English

BRL-49653C

Code

English

AVANDIA

Brand Name

English

Rosiglitazone maleate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98241