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rosiglitazone 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
peroxisome proliferator activating receptor-gamma (PPAR-gamma) agonists, thiazolidinedione derivatives	2405	122320-73-4

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
6	mg	O

ADMET properties:

Property	Value	Reference
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 µM/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:

Date	Agency	Company	Orphan
May 25, 1999	FDA	SB PHARMCO

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Peroxisome proliferator-activated receptor gamma	Nuclear hormone receptor	P37231	PPARG_HUMAN	AGONIST	EC50	7.04	WOMBAT-PK	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	4.53	CHEMBL
Carbonic anhydrase 2	Enzyme	P00918	CAH2_HUMAN		IC50	5.39	DRUG MATRIX
Amine oxidase [flavin-containing] B	Enzyme	P27338	AOFB_HUMAN		Ki	5.38	CHEMBL
Amine oxidase [flavin-containing] A	Enzyme	P21397	AOFA_HUMAN		Ki	4.56	CHEMBL
Peroxisome proliferator-activated receptor alpha	Nuclear hormone receptor	Q07869	PPARA_HUMAN		EC50	7.41	CHEMBL
Retinoic acid receptor RXR-alpha	Nuclear hormone receptor	P19793	RXRA_HUMAN		Kd	4.82	CHEMBL
Retinoic acid receptor gamma	Nuclear hormone receptor	P13631	RARG_HUMAN		Ki	5	CHEMBL
Thromboxane-A synthase	Enzyme	P24557	THAS_HUMAN		IC50	5.45	DRUG MATRIX
Peroxisome proliferator-activated receptor delta	Nuclear hormone receptor	Q03181	PPARD_HUMAN		EC50	5.44	CHEMBL
Free fatty acid receptor 1	GPCR	O14842	FFAR1_HUMAN	AGONIST	EC50	5.60	IUPHAR
Short transient receptor potential channel 5	Ion channel	Q9UL62	TRPC5_HUMAN	ACTIVATOR	EC50	4.51	IUPHAR
Sodium/bile acid cotransporter	Transporter	Q14973	NTCP_HUMAN		IC50	5.29	CHEMBL
CDGSH iron-sulfur domain-containing protein 1	Unclassified	Q9NZ45	CISD1_HUMAN		Ki	7.51	CHEMBL
Bile salt export pump	Transporter	O95342	ABCBB_HUMAN		IC50	5.19	CHEMBL
CDGSH iron-sulfur domain-containing protein 2	Unclassified	Q8N5K1	CISD2_HUMAN		IC50	5.64	CHEMBL
Amine oxidase [flavin-containing] B	Enzyme		AOFB_RAT		Ki	5.24	CHEMBL
Amine oxidase [flavin-containing] A	Enzyme		AOFA_RAT		Ki	4.49	CHEMBL
Peroxisome proliferator-activated receptor alpha	Transcription factor		PPARA_MOUSE		IC50	7.10	CHEMBL
Peroxisome proliferator-activated receptor gamma	Transcription factor		PPARG_MOUSE		EC50	7.52	CHEMBL
Type-1A angiotensin II receptor	GPCR		AGTRA_RAT		Ki	9.64	CHEMBL
Bile salt export pump	Transporter		ABCBB_RAT		IC50	4.40	CHEMBL
CDGSH iron-sulfur domain-containing protein 1	Unclassified		CISD1_RAT		IC50	5.96	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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