rosiglitazone ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
peroxisome proliferator activating receptor-gamma (PPAR-gamma) agonists, thiazolidinedione derivatives 2405 122320-73-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • rosiglitazone
  • rosiglitazone maleate
  • rosiglizole
  • rosiglitazone hydrochloride
  • rosiglitazone HCl
A thiazolidinedione that functions as a selective agonist for PPAR GAMMA. It improves INSULIN SENSITIVITY in adipose tissue, skeletal muscle, and the liver of patients with TYPE 2 DIABETES MELLITUS.
  • Molecular weight: 357.43
  • Formula: C18H19N3O3S
  • CLOGP: 3.02
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 1
  • TPSA: 71.53
  • ALOGS: -3.97
  • ROTB: 7

  • Status: OFM

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
6 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ
S (Water solubility) 0.03 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.37 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 99 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.20 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.65 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.90 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 25, 1999 FDA SB PHARMCO

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Cardiac failure congestive 17336.53 163.83 4181 14752 88252 63381837
Myocardial infarction 14015.79 163.83 3593 15340 96300 63373789
Coronary artery disease 6318.46 163.83 1535 17398 30842 63439247
Cerebrovascular accident 5932.63 163.83 1890 17043 106134 63363955
Acute myocardial infarction 2860.40 163.83 821 18112 31303 63438786
Coronary arterial stent insertion 1763.87 163.83 350 18583 2479 63467610
Coronary artery bypass 1213.71 163.83 249 18684 2120 63467969
Angina unstable 1028.68 163.83 267 18666 6828 63463261
Myocardial ischaemia 791.41 163.83 248 18685 12611 63457478
Vascular graft 523.64 163.83 104 18829 735 63469354
Transient ischaemic attack 516.17 163.83 243 18690 37510 63432579
Angina pectoris 513.45 163.83 226 18707 29852 63440237
Chest pain 450.56 163.83 428 18505 215531 63254558
Cardio-respiratory arrest 431.40 163.83 251 18682 59708 63410381
Arteriosclerosis 389.92 163.83 137 18796 9929 63460160
Acute coronary syndrome 381.50 163.83 135 18798 9991 63460098
Atrial fibrillation 340.37 163.83 280 18653 116356 63353733
Cardiomyopathy 335.48 163.83 143 18790 17441 63452648
Arteriosclerosis coronary artery 332.11 163.83 116 18817 8257 63461832
Sudden cardiac death 326.74 163.83 84 18849 2056 63468033
Ischaemic cardiomyopathy 314.56 163.83 84 18849 2393 63467696
Drug ineffective 280.47 163.83 7 18926 1044758 62425331
Cardiac arrest 248.74 163.83 212 18721 92333 63377756
Cardiac disorder 223.41 163.83 156 18777 50660 63419429
Nausea 210.83 163.83 11 18922 854460 62615629
Fatigue 192.18 163.83 21 18912 888007 62582082
Off label use 182.49 163.83 4 18929 674458 62795631
Diarrhoea 176.95 163.83 9 18924 715357 62754732

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myocardial infarction 18813.21 279.25 5712 19997 115373 34815849
Cardiac failure congestive 14507.41 279.25 4321 21388 78949 34852273
Coronary artery disease 9256.30 279.25 2719 22990 45586 34885636
Cerebrovascular accident 5437.49 279.25 2102 23607 82709 34848513
Acute myocardial infarction 3595.15 279.25 1379 24330 52340 34878882
Coronary artery bypass 2738.29 279.25 650 25059 4252 34926970
Coronary arterial stent insertion 2666.90 279.25 616 25093 3513 34927709
Angina unstable 1195.32 279.25 412 25297 11241 34919981
Myocardial ischaemia 866.34 279.25 363 25346 17045 34914177
Vascular graft 807.94 279.25 194 25515 1328 34929894
Ischaemic cardiomyopathy 631.80 279.25 220 25489 6169 34925053
Arteriosclerosis coronary artery 530.63 279.25 233 25476 12252 34918970
Angina pectoris 496.77 279.25 301 25408 31062 34900160
Transient ischaemic attack 473.65 279.25 279 25430 27334 34903888
Acute coronary syndrome 450.09 279.25 213 25496 13332 34917890
Arteriosclerosis 424.82 279.25 197 25512 11771 34919451
Cardio-respiratory arrest 347.64 279.25 303 25406 54970 34876252
Cardiomyopathy 333.95 279.25 187 25522 16621 34914601
Sudden cardiac death 299.85 279.25 110 25599 3591 34927631
Atrial fibrillation 294.53 279.25 404 25305 121989 34809233
Off label use 293.47 279.25 3 25706 419521 34511701

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Myocardial infarction 30885.07 302.72 8330 28745 175799 79531514
Cardiac failure congestive 28852.58 302.72 7502 29573 134900 79572413
Coronary artery disease 12380.90 302.72 3308 33767 62166 79645147
Cerebrovascular accident 10944.35 302.72 3656 33419 151636 79555677
Acute myocardial infarction 6424.65 302.72 2071 35004 74965 79632348
Coronary arterial stent insertion 4521.18 302.72 937 36138 5107 79702206
Coronary artery bypass 3975.20 302.72 843 36232 5219 79702094
Angina unstable 1940.00 302.72 580 36495 15947 79691366
Vascular graft 1327.20 302.72 282 36793 1749 79705564
Myocardial ischaemia 1303.53 302.72 478 36597 25041 79682272
Angina pectoris 868.21 302.72 441 36634 51291 79656022
Transient ischaemic attack 791.55 302.72 417 36658 52278 79655035
Cardio-respiratory arrest 693.11 302.72 497 36578 108013 79599300
Arteriosclerosis 680.92 302.72 272 36803 17955 79689358
Acute coronary syndrome 675.49 302.72 282 36793 20851 79686462
Chest pain 650.12 302.72 725 36350 281579 79425734
Sudden cardiac death 533.82 302.72 165 36910 5060 79702253
Arteriosclerosis coronary artery 513.65 302.72 221 36854 17595 79689718
Ischaemic cardiomyopathy 501.96 302.72 173 36902 7522 79699791
Drug ineffective 473.33 302.72 6 37069 1080907 78626406
Cardiomyopathy 404.36 302.72 218 36857 28556 79678757
Nausea 403.50 302.72 9 37066 957187 78750126
Cardiac arrest 395.23 302.72 442 36633 171654 79535659
Atrial fibrillation 374.17 302.72 460 36615 197426 79509887
Fatigue 365.86 302.72 16 37059 929711 78777602
Diarrhoea 364.41 302.72 10 37065 880479 78826834

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A10BD03 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BD04 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BG02 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Thiazolidinediones
FDA CS M0199114 PPAR gamma
FDA CS M0447306 Thiazolidinediones
FDA MoA N0000175374 Peroxisome Proliferator-activated Receptor Activity
FDA MoA N0000175377 Peroxisome Proliferator-activated Receptor gamma Agonists
MeSH PA D007004 Hypoglycemic Agents
FDA EPC N0000180186 Peroxisome Proliferator Receptor gamma Agonist
FDA EPC N0000180190 Thiazolidinedione
CHEBI has role CHEBI:50864 insulin sensitizers
CHEBI has role CHEBI:83157 EC 6.2.1.3 inhibitors
CHEBI has role CHEBI:173084 ferroptosis inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Treatment Refractory Type 2 Diabetes Mellitus indication
Alcoholism contraindication 7200002
Weight gain finding contraindication 8943002
Asthenia contraindication 13791008
Pulmonary edema contraindication 19242006 DOID:11396
Myocardial infarction contraindication 22298006 DOID:5844
Acute vomiting contraindication 23971007
Alcohol intoxication contraindication 25702006
Shock contraindication 27942005
Dehydration contraindication 34095006
Macular retinal edema contraindication 37231002 DOID:4449
Infectious disease contraindication 40733004
Body fluid retention contraindication 43498006
Chronic heart failure contraindication 48447003
Hepatic porphyria contraindication 55056006 DOID:3133
Ketoacidosis contraindication 56051008
Metabolic acidosis contraindication 59455009
Hemolytic anemia contraindication 61261009 DOID:583
Glucose-6-phosphate dehydrogenase deficiency anemia contraindication 62403005
Osteoporosis contraindication 64859006 DOID:11476
Hypopituitarism contraindication 74728003 DOID:9406
Cardiogenic shock contraindication 89138009
Kidney disease contraindication 90708001 DOID:557
Lactic acidosis contraindication 91273001 DOID:3650
Fracture of bone contraindication 125605004
Autonomic dysreflexia contraindication 129618003
Liver function tests abnormal contraindication 166603001
Cobalamin deficiency contraindication 190634004
Angina pectoris contraindication 194828000
Decompensated cardiac failure contraindication 195111005
Cerebrovascular accident contraindication 230690007
Disease of liver contraindication 235856003 DOID:409
Drug-induced hepatitis contraindication 235876009
Hypoglycemic disorder contraindication 237630007
Sepsis syndrome contraindication 238150007
Osteopenia contraindication 312894000
Primary adrenocortical insufficiency contraindication 373662000
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Fever contraindication 386661006
Surgical procedure contraindication 387713003
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Myocardial ischemia contraindication 414795007 DOID:3393
Traumatic injury contraindication 417746004
Fever greater than 100.4 Fahrenheit contraindication 426000000
Radiography with IV Iodinated Contrast Agent contraindication
Severe Hypoxemia contraindication




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.5 acidic
pKa2 5.84 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Peroxisome proliferator-activated receptor gamma Nuclear hormone receptor AGONIST EC50 7.04 WOMBAT-PK CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 4.53 CHEMBL
Carbonic anhydrase 2 Enzyme IC50 5.39 DRUG MATRIX
Amine oxidase [flavin-containing] B Enzyme Ki 5.38 CHEMBL
Amine oxidase [flavin-containing] A Enzyme Ki 4.56 CHEMBL
Peroxisome proliferator-activated receptor alpha Nuclear hormone receptor EC50 7.41 CHEMBL
Retinoic acid receptor RXR-alpha Nuclear hormone receptor Kd 4.82 CHEMBL
Retinoic acid receptor gamma Nuclear hormone receptor Ki 5 CHEMBL
Thromboxane-A synthase Enzyme IC50 5.45 DRUG MATRIX
Peroxisome proliferator-activated receptor delta Nuclear hormone receptor EC50 5.44 CHEMBL
Free fatty acid receptor 1 GPCR AGONIST EC50 5.60 IUPHAR
Short transient receptor potential channel 5 Ion channel ACTIVATOR EC50 4.51 IUPHAR
Sodium/bile acid cotransporter Transporter IC50 5.29 CHEMBL
CDGSH iron-sulfur domain-containing protein 1 Unclassified Ki 7.51 CHEMBL
Bile salt export pump Transporter IC50 5.19 CHEMBL
CDGSH iron-sulfur domain-containing protein 2 Unclassified IC50 5.64 CHEMBL
Amine oxidase [flavin-containing] B Enzyme Ki 5.24 CHEMBL
Amine oxidase [flavin-containing] A Enzyme Ki 4.49 CHEMBL
Peroxisome proliferator-activated receptor alpha Transcription factor IC50 7.10 CHEMBL
Peroxisome proliferator-activated receptor gamma Transcription factor EC50 7.52 CHEMBL
Type-1A angiotensin II receptor GPCR Ki 9.64 CHEMBL
Bile salt export pump Transporter IC50 4.40 CHEMBL
CDGSH iron-sulfur domain-containing protein 1 Unclassified IC50 5.96 CHEMBL

External reference:

IDSource
4021162 VUID
N0000148613 NUI
D00596 KEGG_DRUG
155141-29-0 SECONDARY_CAS_RN
4021162 VANDF
4021163 VANDF
C0289313 UMLSCUI
CHEBI:50122 CHEBI
BRL PDB_CHEM_ID
CHEMBL121 ChEMBL_ID
DB00412 DRUGBANK_ID
CHEMBL843 ChEMBL_ID
D000077154 MESH_DESCRIPTOR_UI
77999 PUBCHEM_CID
1056 IUPHAR_LIGAND_ID
7662 INN_ID
302543-62-0 SECONDARY_CAS_RN
05V02F2KDG UNII
253198 RXNORM
8221 MMSL
d04434 MMSL
007789 NDDF
007790 NDDF
116096001 SNOMEDCT_US
326053005 SNOMEDCT_US
395869000 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Avandia HUMAN PRESCRIPTION DRUG LABEL 1 54868-4198 TABLET, FILM COATED 4 mg ORAL NDA 19 sections
Avandia HUMAN PRESCRIPTION DRUG LABEL 1 54868-4221 TABLET, FILM COATED 8 mg ORAL NDA 19 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-4965 TABLET, FILM COATED 2 mg ORAL NDA 30 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5157 TABLET, FILM COATED 4 mg ORAL NDA 30 sections
Avandia HUMAN PRESCRIPTION DRUG LABEL 1 54868-5249 TABLET, FILM COATED 2 mg ORAL NDA 19 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5262 TABLET, FILM COATED 4 mg ORAL NDA 30 sections
AVANDAMET HUMAN PRESCRIPTION DRUG LABEL 2 54868-5376 TABLET, FILM COATED 2 mg ORAL NDA 30 sections