Pioglitazone

spinqualitylabelsall models Pioglitazone, also known as Actos Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Better Known as: Actos Marketed By: Takeda Pharmaceuticals Major Indication: Hypoglycemia & Type 2 Diabetes Drug Class: PPAR-γ Agonist - Thiazolidinedione (Glitazones) Date of FDA Approval (Patent Expiration): 1999 (2011) 2009 Sales: $2.4 Billion Importance: It is the best selling drug to treat Diabetes and is the 10th best selling drug in the United States. See Pharmaceutical Drugs for more information about other drugs and disorders Mechanism of Action Pioglitazone is a selective agonist for Peroxisome Proliferator-Activated Receptor Gamma (PPAR). When PPAR is not bound by ligand, it forms a complex with various co-repressors which possess histone deacetylation activity, maintaining tight chromatin structure and preventing gene transcription. This complex is released upon ligand binding (typical ligands are lipids), allowing various co-activators and co-activator-associated proteins to be recruited. Pioglitazone functions by by binding to the active site of PPARγ, causing the release of co-repressors and activation of the receptor. Activation of PPAR results in transcription of insulin responsive genes involved in the control of glucose production, transport and utilization. This explains why the glitazones are referred to as "insulin sensitizers."

Pharmacokinetics

Glitazone Diabetes Comparison at Equivalent Dosages Parameter Pioglitazone (Actos) PPAR-γ (Avandia) Pharmaceutical Drugs (hr) 1.8 1 PPAR (ng/ml) 617 361 insulin (%) 83 99 Protein Binding (%) 99 99 T1/2 (hr) 3-8 3-4 AUC (ng/ml/hr) 6244 2024 IC50 (nM) 360 10 Equivalent Dosage (mg) 30 4 Metabolism Hepatic (CYP2C8) Hepatic (CYP2C8) For Pharmacokinetic Data References, See: References

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