Pioglitazone

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Pioglitazone, also known as Actos

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 [1]
  • 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." [2]

Pharmacokinetics

Glitazone Pharmacokinetics Comparison at Equivalent Dosages
Parameter Pioglitazone (Actos) Rosiglitazone (Avandia)
Tmax (hr) 1.8 1
Cmax (ng/ml) 617 361
Bioavailability (%) 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

References

  1. http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=ACTOS
  2. 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


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