My watch list
my.bionity.com  
Login  

Pioglitazone



Pioglitazone
Systematic (IUPAC) name
5-((4-(2-(5-ethyl-2-pyridinyl)
ethoxy)phenyl)methyl)-,(+-)-
2,4-thiazolidinedione,
Identifiers
CAS number 111025-46-8
ATC code A10BG03
PubChem 4829
DrugBank APRD00653
Chemical data
Formula C19H20N2O3S 
Mol. mass 356.44 g/mol
Pharmacokinetic data
Bioavailability  ?
Protein binding >99%
Metabolism liver (CYP2C8)
Half life 3–7 hours
Excretion in bile
Therapeutic considerations
Licence data

EU US

Pregnancy cat.

C

Legal status

PoM (UK), Rx (US)

Routes oral

Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic (antihyperglycemic, antidiabetic) action. Pioglitazone is marketed as trademarks Actos in the USA and Glustin in Europe by the pharmaceutical company Takeda.

Additional recommended knowledge

Contents

Pharmacology

Pioglitazone selectively stimulates nuclear receptor peroxisone proliferator-activated receptor gamma (PPARγ). It modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the lipidic, muscular tissues and in the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues; increases the expense of insulin-dependent glucose; decreases withdrawal of glucose from the liver; reduces quantity of glucose, insulin and glycated haemoglobin in the bloodstream. Although not clinically significant, pioglitazone decreases the level of triglycerides and increases that of high-density lipoproteins (HDL) without changing low-density lipoproteins (LDL) and total cholesterol in patients with disorders of the lipid metabolism, although statins are the drug of choice for this.

More recently, pioglitazone and other active TZDs have been shown to bind to the outer mitochondrial membrane protein mitoNEET with affinity comparable to that of pioglitazone for PPARγ.[1][2]

Indications and usage

Pioglitazone is used for the treatment of diabetes mellitus type 2 (non-insulin-dependent diabetes mellitus, NIDDM) in monotherapy but usually in combination with sulfonylurea, metformin, or insulin. Pioglitazone has also been used to treat non-alcoholic steatohepatitis (fatty liver), but this use is presently considered experimental.[3]

Contraindications

Pioglitazone cannot be used in patients with a known hypersensitivity to pioglitazone, other thiazolidinediones or any of components of its pharmaceutical forms. It is ineffective and possibly harmful in diabetes mellitus type 1 and diabetic ketoacidosis. Its safety in pregnancy, lactation (breastfeeding) and people under 18 is not established.

Given previous experiences with the related drug troglitazone, acute diseases of the liver are regarded as a contraindication for pioglitazone.

Side effects

A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide.[3] The information was based on data from the ADOPT trial.[4] Following release of this statement, Takeda also admitted that pioglitazone has similar implications for female patients.

The risk of hypoglycemia is low in the absence of other drugs that lower blood glucose.

Like other thiazolidinediones, pioglitazone can cause fluid retention and peripheral edema. As a result, it may precipitate congestive heart failure (which worsens with fluid overload in those at risk). It may cause anemia. Mild weight gain is common due to increase in subcutaneous adipose tissue. In studies, patients on pioglitazone had a slightly increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems. On July 30, 2007 an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of "myocardial ischemic events". The FDA Advisory Committee are currently reviewing rosiglitazone data following an initial rejection of submitted data. Pioglitazone was not reviewed. A meta-analysis released subsequently showed that pioglitazone reduced the number of ischemic cardiac events rather than increase the risk.[4]

Drug interactions

Sulfonamides, metformin, and insulin reciprocally exponentiate hypoglycemia. Therapy with pioglitazone increased risk for pregnancy in those taking oral contraception.

How supplied

Pioglitazone as Actos is supplied in oral tablets containing 15, 30 or 45 mg of pioglitazone base, however it should be noted that 15 mg is a subtherapeutic dose, with 30 mg the starting dose. It is also available in combination with metformin as ActoplusMet (tablets containing 15 mg pioglitazone and either 500 or 850 mg of metformin) or in combination with Amaryl as Duetact (tablets containing 30 mg pioglitazone and either 2 or 4 mg of Amaryl).

References

  1. ^ Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR (2004). "Identification of a novel mitochondrial protein ("mitoNEET") cross-linked specifically by a thiazolidinedione photoprobe". Am. J. Physiol. Endocrinol. Metab. 286 (2): E252-60. doi:10.1152/ajpendo.00424.2003. PMID 14570702.
  2. ^ Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA (2007). "MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone". Proc. Natl. Acad. Sci. U.S.A. 104 (36): 14342-7. doi:10.1073/pnas.0707189104. PMID 17766440.
  3. ^ Belfort R, Harrison SA, Brown K, et al. (2006). "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis" 355 (22): 2297–307.
  4. ^ Lincoff AM, Wolski K, Nicholls SJ, Nissen SE (2007). "Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials". JAMA 298 (10): 1180-8. doi:10.1001/jama.298.10.1180. PMID 17848652.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Pioglitazone". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE