TROGLITAZONE

US Previously Marketed

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12475986 | http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf

Troglitazone (TGZ, brand name: Rezulin and Prelay) is a peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand, which was developed by Daiichi Sankyo and approved for the US market for the treatment of Type II diabetes mellitus. The drug is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise, and was not indicated as initial therapy in patients with type 2 diabetes. This drug was withdrawn from the UK market due to liver toxicity. It was removed from the US market in 2000, only 3 years after its introduction and from Japan, shortly afterward. In addition, was conducted a clinical trial for the treatment of patients with advanced liposarcoma by using troglitazone, but the positive result wasn’t obtained. It was shown, that in case of cancer cells troglitazone acted independently of PPAR gamma, by up-regulation of early growth response-1 (Egr-1). Egr-1 transcription factor has been linked to apoptosis and shown to be activated by extracellular signal-regulated kinase (ERK).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor gamma 118 Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10691680	Agonist 2752		780.0 nM [EC50]
Early growth response protein 1 1 Target ID: P18146 Gene ID: 1958.0 Gene Symbol: EGR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12475986	Activator 1447

Conditions

Condition	Modality	Highest Phase	Product
Polycystic ovary syndrome 2 Sources: https://adisinsight.springer.com/drugs/800000013 https://www.ncbi.nlm.nih.gov/pubmed/21105563 https://www.ncbi.nlm.nih.gov/pubmed/15767238	Primary	Phase III 665	Unknown Approved Use Unknown
Type 2 diabetes mellitus 262 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf	Palliative	Withdrawn	PRELAY Approved Use Prelay is indicated to improve glycemic control in patients with type 2 diabetes mellitus as an adjunct to diet and exercise in combination with (not substituted for): · A sulfonylurea drug for patients who are not adequately controlled with a sulfonylurea alone or, · A sulfonylurea drug together with metformin for patients who are not adequately controlled with the combination of a sulfonylurea and metformin or, · Insulin in patients who are not adequately controlled with insulin alone. Prelay is not indicated as initial therapy in patients with type 2 diabetes Launch Date 1997
Liposarcoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10097144	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.9 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3 \| https://pubmed.ncbi.nlm.nih.gov/10471982/	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.61 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3 \| https://pubmed.ncbi.nlm.nih.gov/10471982/	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.82 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3 \| https://pubmed.ncbi.nlm.nih.gov/10471982/	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.01 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.74 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
7.4 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3 \| https://pubmed.ncbi.nlm.nih.gov/10471982/	200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
13.4 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3 \| https://pubmed.ncbi.nlm.nih.gov/10471982/	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
22.1 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3 \| https://pubmed.ncbi.nlm.nih.gov/10471982/	600 mg 1 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
7.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
10.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
8.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
34 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20720s12lbl.pdf#page=3		TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
12.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
13.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

F_unbound

Value	Dose	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20719S12_Prelay_prntlbl.pdf#page=3		TROGLITAZONE serum	Homo sapiens
2.6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9832300/	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TROGLITAZONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
800 mg 1 times / day multiple, oral Highest studied dose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12846423/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/12846423/	Disc. AE: Vomiting... Other AEs: Nausea, Anorexia... AEs leading to discontinuation/dose reduction: Vomiting (grade 2, 9%) Other AEs: Nausea (grade 1-2, 41%) Anorexia (grade 1, 9%) Diarrhea (grade 1, 9%) Dyspepsia (grade 1-2, 18%) Transaminases increased (grade 1-2, 9%) Alkaline phosphatase increased (grade 1-3, 14%) Mental status changes (grade 4, 4.5%) Cranial neuropathy (grade 2, 4.5%) Constipation (grade 1, 4.5%) Pain (grade 1-2, 32%) Bone pain (grade 1-3, 18%) Fatigue (grade 1-2, 14%) Anxiety (grade 2, 9%) Insomnia (grade 2, 4.5%) Wound infection (grade 3, 4.5%) Hemoglobin abnormal (grade 1, 9%) Hyperglycemia (grade 1, 4.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/12846423/
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9652997/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9652997/	Disc. AE: Hepatitis drug-induced... AEs leading to discontinuation/dose reduction: Hepatitis drug-induced (grade 3) Sources: https://pubmed.ncbi.nlm.nih.gov/9652997/
400 mg 1 times / day multiple, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9652998/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9652998/	Disc. AE: Hepatic failure... AEs leading to discontinuation/dose reduction: Hepatic failure Sources: https://pubmed.ncbi.nlm.nih.gov/9652998/

AEs

PubMed

Title	Date	PubMed
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition.	2003-04	12642470
A cohort study of the incidence of serious acute liver injury in diabetic patients treated with hypoglycemic agents.	2003-03-24	12639207
Troglitazone but not rosiglitazone induces G1 cell cycle arrest and apoptosis in human and rat hepatoma cell lines.	2003-03-20	12595159
Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma ) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma. A novel mechanism for its anti-tumorigenic activity.	2003-02-21	12475986
The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial.	2003-02	12601628
Receptor-dependent regulation of the CYP3A4 gene.	2002-12-27	12505310
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation suppresses ischemic induction of Egr-1 and its inflammatory gene targets.	2002-12	12468449
Effects of leptin, troglitazone, and dietary fat on stearoyl CoA desaturase.	2002-10-11	12372423
Troglitazone induces G1 arrest by p27(Kip1) induction that is mediated by inhibition of proteasome in human gastric cancer cells.	2002-07	12149143
Nonsteroidal anti-inflammatory drugs induce apoptosis in association with activation of peroxisome proliferator-activated receptor gamma in rheumatoid synovial cells.	2002-07	12065695
PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages.	2002-06-05	12044893
Troglitazone improves GLUT4 expression in adipose tissue in an animal model of obese type 2 diabetes mellitus.	2002-06	11947963
Troglitazone activates p21Cip/WAF1 through the ERK pathway in HCT15 human colorectal cancer cells.	2002-05-28	11888673
Troglitazone treatment of aging Brown Norway rats improves food intake and weight gain after fasting without increasing hypothalamic NPY gene expression.	2002-05	11909685
Concentration-dependent stimulatory and inhibitory effect of troglitazone on insulin-induced fatty acid synthase expression and protein kinase B activity in 3T3-L1 adipocytes.	2002-04	11919653
Troglitazone suppresses the secretion of type I collagen by mesangial cells in vitro.	2002-04	11918743
Troglitazone downregulates delta-6 desaturase gene expression in human skeletal muscle cell cultures.	2002-04	11916926
Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat.	2002-04	11912544
Effects of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT) on 3T3-L1 and 3T3-F442A adipocyte differentiation.	2002-03-01	11911853
Troglitazone, an insulin-sensitizing thiazolidinedione, represses combined stimulation by LH and insulin of de novo androgen biosynthesis by thecal cells in vitro.	2002-03	11889176
Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma.	2002-02-01	11834241
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002-01-11	11779144
Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons.	2002-01-11	11750908
Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes.	2002-01	11752099
Growth inhibition and differentiation of pancreatic cancer cell lines by PPAR gamma ligand troglitazone.	2002-01	11741176
Regulation of the glyoxalase pathway in human brain microvascular endothelium: effects of troglitazone and tertiary butylhydroperoxide.	2002	12572858
15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells.	2001-12-28	11687581
Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors.	2001-11	11768731
Troglitazone selectively inhibits glyoxalase I gene expression.	2001-11	11719831
Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by troglitazone: a peroxisome proliferator-activated receptor-gamma (PPARgamma)-independent, antioxidant-related mechanism.	2001-10-15	11597575
Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate.	2001-10-05	11557132
Arylhydrocarbon receptor (AhR) is involved in negative regulation of adipose differentiation in 3T3-L1 cells: AhR inhibits adipose differentiation independently of dioxin.	2001-08	11683414
15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways.	2001-07-13	11457450
Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action?	2001-07	11443197
Severe cholestatic hepatitis from troglitazone in a patient with nonalcoholic steatohepatitis and diabetes mellitus.	2001-05	11374713
Involvement of p21(WAF1/Cip1), p27(Kip1), and p18(INK4c) in troglitazone-induced cell-cycle arrest in human hepatoma cell lines.	2001-05	11343236
Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes.	2001-05	11334422
Troglitazone induces GLUT4 translocation in L6 myotubes.	2001-05	11334413
Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats.	2001-05	11318962
Peroxisome proliferator-activated receptor gamma ligands suppress the transcriptional activation of cyclooxygenase-2. Evidence for involvement of activator protein-1 and CREB-binding protein/p300.	2001-04-13	11278336
Dual function of troglitazone in ICAM-1 gene expression in human vascular endothelium.	2001-04-06	11401521
Troglitazone, a ligand for peroxisome proliferator-activated receptor gamma, inhibits chemically-induced aberrant crypt foci in rats.	2001-04	11346461
Effect of obesity and troglitazone on expression of two glutathione peroxidases: cellular and extracellular types in serum, kidney and adipose tissue.	2001-04	11328671
Bezafibrate attenuates the overexpression of plasminogen activator inhibitor-1 messenger RNA by a combination of mono-unsaturated fatty acid and insulin in hepG2 cells.	2001-03-09	11292061
Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL.	2001-03	11231916
Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin.	2001-02	11281188
Abundant expression of uncoupling protein-2 in the small intestine: up-regulation by dietary fish oil and fibrates.	2001-01-15	11341955
Effects of type-2 diabetes and troglitazone on the expression patterns of small intestinal sugar transporters and PPAR-gamma in the Zucker diabetic fatty rat.	2001	11244250
Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone.	2000-12	11228057
Troglitazone, a PPARgamma ligand, inhibits osteopontin gene expression in human monocytes/macrophage THP-1 cells.	2000	11426586

Patents

Sample Use Guides

In Vivo Use Guide

Prelay (TROGLITAZONE tablet) should be taken with a meal. Combination Therapy: Sulfonylureas: Prelay in combination with a sulfonylurea should be initiated at 200 mg once daily. The current sulfonylurea dose should be continued upon initiation of Prelay therapy. For patients not responding adequately, the Rezulin dose should be increased at 2 to 4 weeks. The maximum recommended dose is 600 mg once daily. The dose of sulfonylurea may require lowering to optimize therapy. Metformin: For patients not responding adequately to metformin and sulfonylurea therapy, 400 mg daily of Prelay may be added. Insulin: The current insulin dose should be continued upon initiation of Prelay therapy. Prelay therapy should be initiated at 200 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Prelay should be increased after approximately 2 to 4 weeks. The usual dose of Prelay is 400 mg once daily. The maximum recommended daily dose is 600 mg. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and Prelay. Further adjustments should be individualized based on glucose-lowering response. Patients With Renal Insufficiency: Dose adjustment in patients with renal insufficiency is not required

Route of Administration: Oral

In Vitro Use Guide

Human HCC cell lines Huh7 and Hep3B were cultured in the presence or absence of troglitazone. Cell growth was determined via WST-1 assay, proliferation by cell cycle analysis and proliferating cell nuclear antigen (PCNA) Western blotting, and apoptosis by flow cytometry and TUNEL. In cultures of Hep3B and Huh7 cells, basal expression of PPARgamma was relatively low, but troglitazone caused dose-dependent induction of PPARgamma expression.

Substance Class	Mixture Created by `admin` on `Mon Mar 31 18:33:28 GMT 2025` Edited by `admin` on `Mon Mar 31 18:33:28 GMT 2025`
Record UNII	I66ZZ0ZN0E
Record Status	`FAILED`
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Name

Type

Language

TROGLITAZONE

Official Name

English

PRELAY

Preferred Name

English

TROGLITAZONE [USAN]

Common Name

English

TROGLITAZONE [JAN]

Common Name

English

TROGLITAZONE [MI]

Common Name

English

CS-045

Code

English

TROGLITAZONE [MART.]

Common Name

English

Troglitazone [WHO-DD]

Common Name

English

REZULIN

Brand Name

English

TROGLITAZONE [VANDF]

Common Name

English

CI-991

Code

English

2,4-THIAZOLIDINEDIONE, 5-((4-((3,4-DIHYDRO-6-HYDROXY-2,5,7,8-TETRAMETHYL-2H-1-BENZOPYRAN-2-YL)METHOXY)PHENYL)METHYL)-

Common Name

English

troglitazone [INN]

Common Name

English

GR92132X

Code

English

GR-92132X

Code

English

TROGLITAZONE [ORANGE BOOK]

Common Name

English

(±)-ALL-RAC-5-(P-((6-HYDROXY-2,5,7,8-TETRAMETHYL-2-CHROMANYL)METHOXY)BENZYL)-2,4-THIAZOLIDINEDIONE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1934