- Overview
- Properties
- Genetics
- Related Genes
- Pathways
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
Overview
| Generic Names: | Rosigliazone maleate; Rosiglitazone maleate; rosiglitazone |
|---|---|
| Trade Names: | Avandia; Rosiglizole |
| Brand Mixtures: | Avandamet (Metformin hydrochloride + Rosiglitazone maleate); Avandaryl (Glimepiride + Rosiglitazone maleate) |
| PharmGKB Accession Id: | PA451283 |
Description
Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl).
Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action.
Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone.
Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele. This is the subject of a clinical trial currently underway.
(source:
Drug Bank)
Indication
For the treatment of Type II diabetes mellitus (source: Drug Bank)
ATC Therapeutic Category
- A10BG:Thiazolidinediones
Pharmacology, Interactions, and Contraindications
Mechanism Of Action
Rosiglitazone acts as an agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, rosiglitazone enhances tissue sensitivity to insulin. (source: Drug Bank)
Pharmacology
Rosiglitazone, a member of the drug group known as the thiazolidinediones or "insulin sensitizers", is not chemically or functionally related to the alpha-glucosidase inhibitors, the biguanides, or the sulfonylureas. Rosiglitazone targets insulin resistance and, hence, is used alone or with metformine or sulfonylurea to improve glycemic control in patients with type 2 diabetes mellitus. (source: Drug Bank)
Absorption, Distribution, Metabolism, Elimination & Toxicity
Biotransformation
Hepatic. Rosiglitazone is extensively metabolized in the liver to inactive metabolites via N-demethylation, hydroxylation, and conjugation with sulfate and glucuronic acid. In vitro data have shown that Cytochrome (CYP) P450 isoenzyme 2C8 (CYP2C8) and to a minor extent CYP2C9 are involved in the hepatic metabolism of rosiglitazone. (source: Drug Bank)
Protein Binding
99.8% bound to plasma proteins, primarily albumin. (source: Drug Bank)
Absorption
The absolute bioavailability of rosiglitazone is 99%. Peak plasma concentrations are observed about 1 hour after dosing. Administration of rosiglitazone with food resulted in no change in overall exposure (AUC), but there was an approximately 28% decrease in C<sub>max</sub> and a delay in T<sub>max</sub> (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food. (source: Drug Bank)
Toxicity
Side effects include fluid retention, congestive heart failure (CHF), liver disease (source: Drug Bank)
Isomeric SMILES Code:
CN(CCOC1=CC=C(C=C1)C[C@@H]2C(=O)NC(=O)S2)C3=CC=CC=N3 (source: Drug Bank)
Curated Annotations (
)
-
rs10192566
at chr2:11807879
in
LPIN1
A study in patients with type 2 diabetes treated with rosiglitazone showed that this SNP in the LPIN1 gene was significantly associated with rosiglitazone treatment response. rs11693809 and rs2278513 are in nearly complete linkage disequilibrium with rs10192566.- Related Drugs:
- rosiglitazone
- Related Diseases:
- Diabetes Mellitus, Type 2
- Evidence:
-
PMID:18693052
-
rs10509681
at chr10:96788739
in
CYP2C8
Different literature sources show a discrepancy between several in vitro findings describing a lower activity of the CYP2C8*3 variant and in vivo findings showing higher oral clearance in *3 allele carriers at least for some substrates of CYP2C8. A study on healthy volunteers administered with repaglinide found that the CYP2C8*3 variant allele was associated with reduced plasma concentrations of repaglinide. Another study showed that subjects carrying the CYP2C8*3 allele had a lower rosiglitazone plasma concentration.- Variant Name:
- CYP2C8: K399R; A1196G; CYP2C8*3
- Related Drugs:
- repaglinide, rosiglitazone
- Evidence:
-
PMID:14534525
PMID:17178266
-
rs11572080
at chr10:96817020
in
CYP2C8
Different literature sources show a discrepancy between several in vitro findings describing a lower activity of the CYP2C8*3 variant and in vivo findings showing higher oral clearance in *3 allele carriers at last for some substrates ofCYP2C8. A study on healthy volunteers administered with repaglinide found that the CYP2C8*3 variant allele was associated with reduced plasma conentrations of repaglinde. Another study showed that subjects carrying the CYP2C8*3allele had a lower rosiglitazone plasma concentartion.- Variant Name:
- CYP2C8: R139K; G416A; CYP2C8*3
- Related Drugs:
- repaglinide, rosiglitazone
- Evidence:
-
PMID:14534525
PMID:17178266
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
ABCA1 |
|
Publications |
|
ABCB1 |
|
Publications |
|
|
ADIPOQ |
|
Publications |
|
|
AKT1 |
|
Publications |
|
|
APOE |
|
Publications |
|
|
CYP2C8 |
|
Publications, Variants |
|
|
CYP2C9 |
|
Publications |
|
|
FRAP1 |
|
Publications |
|
|
GSK3B |
|
Publications |
|
|
HBA1 |
|
Publications |
|
|
LPIN1 |
|
Publications, Variants |
|
|
MMP9 |
|
Publications |
|
|
NAMPT |
|
Publications |
|
|
NR1I2 |
|
Publications |
|
|
PLIN |
|
Publications |
|
|
PPARG |
|
Publications |
|
|
PRKAA1 |
|
Publications |
|
|
PRKAA2 |
|
Publications |
|
|
PRKAB1 |
|
Publications |
|
|
PRKAB2 |
|
Publications |
|
|
PRKAG1 |
|
Publications |
|
|
PRKAG2 |
|
Publications |
|
|
PTEN |
|
Publications |
|
|
RBP4 |
|
Publications |
|
|
RPS6KB1 |
|
Publications |
|
|
SAA1 |
|
Publications |
|
|
SAA2 |
|
Publications |
|
|
SLCO1B1 |
|
Publications |
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
| Gene | Description | |
|---|---|---|
| PPARG |
|
(source: Drug Bank) |
A list of non-curated publications that mention this drug along with other drugs is available.
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Alzheimer Disease |
|
Publications |
|
|
Diabetes Mellitus |
|
Publications |
|
|
diabetes mellitus type 2 and obesity |
|
Publications |
|
|
Diabetes Mellitus, Type 2 |
|
Publications, Variants |
|
|
HIV |
|
Publications |
|
|
Myocardial Infarction |
|
Publications |
|
|
Obesity |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
Search PubMed
Search Medline Plus
Search PubChem
Search CTD
Non-Curated Publications
A list of non-curated publications that mention this drug is available.