Brands, Medical Use, Clinical Data
- Vasodilator Agents
- Hypoglycemic Agents
- Fibrinolytic Agents
Brands / Synonyms
Avandamet; Avandaryl; Avandia; Rosigliazone maleate; Rosiglitazone maleate; Rosiglizole
For the treatment of Type II diabetes mellitus
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.
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.
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 Cmax and a delay in Tmax (1.75 hours). These changes are not likely to be clinically significant; therefore, rosiglitazone may be administered with or without food.
Side effects include fluid retention, congestive heart failure (CHF), liver disease
Biotrnasformation / Drug Metabolism
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.
AVANDIA is contraindicated in patients with known hypersensitivity to this product or any of its components.
An inhibitor of CYP2C8 (such as gemfibrozil) may increase the AUC of rosiglitazone and an inducer of CYP2C8 (such
as rifampin) may decrease the AUC of rosiglitazone. Therefore, if an inhibitor or an inducer of CYP2C8 is started or
stopped during treatment with rosiglitazone, changes in diabetes treatment may be needed based upon clinical