Rosiglitazone
From Proteopedia
|
Better Known as: Avandia
- Marketed By: GlaxoSmithKline (No Longer Marketed)
- Major Indication: Hypoglycemia & Type 2 Diabetes
- Drug Class: PPAR-γ Activator - Thiazolidinedione (Glitazones)
- Date of FDA Approval (Patent Expiration): 1999 (2012)
- 2009 (2006) Sales: $400 Million ($2.5 Billion)[1]
- Why You Should Care: Once the best selling Diabetes treatment in the world. Lawsuits and legal action being pursued against GlaxoSmithKline for manipulation of clinical data upon which Avandia was approved with regards to its side effect profile.
- The following is a list of Pharmacokinetic Parameters. See: Pharmaceutical Drugs for more information
Mechanism of Action
Rosiglitazone occupies roughly 40% of the LBD. It assumes a U-shaped conformation with the TZD head group forming a number of interactions that stabilize the agonist. Rosiglitazone forms hydrogen bond interactions with H323 and H449 and its TZD group, the sulfur atom of the TZD occupies a hydrophobic pocket formed by Phe363, Glu286, Phe282, Leu330, Ile326 and Leu469, and the central benzene ring occupies a pocket formed by Cys285 and Met364 [2]
Pharmacokinetics
| Glitazone Pharmacokinetics Comparison | |||||
|---|---|---|---|---|---|
| Parameter | Pioglitazone (Actos) | Rosiglitazone (Avandia) | |||
| Tmax (hr) | |||||
| Cmax (ng/ml) | |||||
| Bioavailability (%) | |||||
| Protein Binding (%) | 99 | 99 | |||
| T1/2 (hr) | 3-7 | 3-4 | |||
| AUC (ng/ml/hr) | |||||
| IC50 (nM) | |||||
| Equivalent Dosage (mg) | |||||
| Metabolism | Hepatic (CYP2C8) | Hepatic (CYP2C8) | |||
Effectiveness and Side Effects
Effectiveness
Side Effects
Interesting Facts
The Jist
References
- ↑ http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=AVANDIA
- ↑ Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, Rosenfeld MG, Willson TM, Glass CK, Milburn MV. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature. 1998 Sep 10;395(6698):137-43. PMID:9744270 doi:10.1038/25931
