ROSIGLITAZONE

US Previously Marketed

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

Structure Search

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)

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 118 Target ID: CHEMBL235 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10764590	Agonist 2752		40.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 262 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf	Primary		Approved 8583	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
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
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

AUC

Value	Dose	Co-administered	Analyte	Population
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
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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
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

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	unhealthy, 53.1 Health Status: unhealthy Age Group: 53.1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18503774	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
20 mg single, oral Overdose Dose: 20 mg Route: oral Route: single Dose: 20 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25390127	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/25390127	Disc. AE: Macular edema... AEs leading to discontinuation/dose reduction: Macular edema Sources: https://pubmed.ncbi.nlm.nih.gov/25390127
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf	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

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	unhealthy, 53.1 Health Status: unhealthy Age Group: 53.1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18503774
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	unhealthy, 53.1 Health Status: unhealthy Age Group: 53.1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18503774
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	unhealthy, 53.1 Health Status: unhealthy Age Group: 53.1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18503774
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	unhealthy, 53.1 Health Status: unhealthy Age Group: 53.1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18503774
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	unhealthy, 60 Health Status: unhealthy Age Group: 60 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/25390127
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf

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
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	10871200
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
Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight.	2000 May 10	10799317
Activation of peroxisome proliferator-activated receptor gamma suppresses nuclear factor kappa B-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells.	2001 Aug 17	11397815
Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway.	2001 Feb	11218074
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
Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes.	2001 May	11334422
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
Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation.	2002 Jun	12021203
Rosiglitazone-induced granulomatous hepatitis.	2002 May-Jun	11960075
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
Accelerated hypertension due to rosiglitazone therapy.	2002 Nov-Dec	12674195
A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs.	2003 Feb 7	12565875
Decreased expression of peroxisome proliferator activated receptor gamma in cftr-/- mice.	2004 Aug	15174093
Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats.	2004 Dec 1	15526359
Evidence for a potent antiinflammatory effect of rosiglitazone.	2004 Jun	15181049
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.	2004 May	15089784
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.	2004 Nov	15520860
Rosiglitazone treatment improves insulin regulation and dyslipidemia in type 2 diabetic cynomolgus monkeys.	2004 Sep	15334371
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005 Aug	15860655
Chaperone proteins involved in troglitazone-induced toxicity in human hepatoma cell lines.	2005 Feb	15525695
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
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	15855323
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

Official Name

English

GAUDIL

Preferred Name

English

ROSIGLIZOLE

Brand Name

English

BRL-49653

Code

English

NSC-758698

Code

English

ROSIGLITAZONE [MI]

Common Name

English

rosiglitazone [INN]

Common Name

English

ROSIGLITAZONE [EMA EPAR]

Common Name

English

REZULT

Brand Name

English

TDZ-01

Code

English

ROSIGLITAZONE [VANDF]

Common Name

English

2,4-THIAZOLIDINEDIONE, 5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-

Systematic Name

English

ROSIGLITAZONE [MART.]

Common Name

English

ROSIGLITAZONE [IARC]

Common Name

English

ROSVEL

Brand Name

English

5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-2,4-THIAZOLIDINEDIONE

Systematic Name

English

ROSIGLITAZONE [HSDB]

Common Name

English

Rosiglitazone [WHO-DD]

Common Name

English

5-(4-(2-(N-METHYL-N-(2-PYRIDINYL)AMINO)ETHOXY)BENZYL)-2,4-THIAZOLIDINEDIONE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98241