ROSIGLITAZONE CHOLINATE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H18N3O3S.C5H14NO
Molecular Weight	460.59
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[N+](C)(C)CCO.CN(CCOC1=CC=C(CC2SC(=O)[N-]C2=O)C=C1)C3=CC=CC=N3

InChI

InChIKey=JKQQOKOTRFSCBL-UHFFFAOYSA-M

InChI=1S/C18H19N3O3S.C5H14NO/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;1-6(2,3)4-5-7/h2-9,15H,10-12H2,1H3,(H,20,22,23);7H,4-5H2,1-3H3/q;+1/p-1

HIDE SMILES / InChI

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	( + / - )

Molecular Formula	C5H13NO
Molecular Weight	103.1628
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
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
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
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
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
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
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
Evidence for a potent antiinflammatory effect of rosiglitazone.	2004 Jun	15181049
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
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	15150131
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.	2004 Nov	15520860
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
Chronic heart failure-related interventions after starting rosiglitazone in patients receiving insulin.	2004 Oct	15628829
Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro.	2004 Oct	15491415
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation.	2004 Oct 22	15381068
Rosiglitazone treatment improves insulin regulation and dyslipidemia in type 2 diabetic cynomolgus monkeys.	2004 Sep	15334371
Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors.	2005	15865214
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	15665514
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005 Aug	15860655
Rosiglitazone, PPAR-gamma receptor ligand, decreases the viability of rat prolactin-secreting pituitary tumor cells in vitro.	2005 Feb	15726020
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
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
The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes.	2005 May	15855579
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
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:55:57 GMT 2023` Edited by `admin` on `Fri Dec 15 18:55:57 GMT 2023`
Record UNII	386X2T4SQV
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ROSIGLITAZONE CHOLINATE

Common Name

English

ETHANAMINIUM, 2-HYDROXY-N,N,N-TRIMETHYL-, ((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-2,4-THIAZOLIDINEDIONATE (1:1)

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98241