Rosiglitazone detailed information
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| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Bioavailability | 99% |
| Protein binding | 99.8% |
| Metabolism | Hepatic (CYP2C8-mediated) |
| Elimination half-life | 3-4 hours |
| Excretion | Renal (64%) and fecal (23%) |
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| E number | {{#property:P628}} |
| ECHA InfoCard | {{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value). |
| Chemical and physical data | |
| Formula | C18H19N3O3S |
| Molar mass | 357.428 g/mol |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl).
Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ, and has no PPARα-binding action.
Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFκB) levels fall and inhibitor (IκB) levels increase in patients on rosiglitazone.[1]
Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele.[2] This is the subject of a clinical trial currently underway.
Side-effects and contraindications
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]
An article by Dr. Steven Nissen and his colleague Kathy Wolski in the June 14, 2007 issue of The New England Journal of Medicine reported that the use of rosiglitazone was associated with a slightly increased risk of heart attack (odds ratio=1.43).[5][6] The FDA issued an alert on May 21 2007.[7] The findings of the study by Stevens and Wolski were considered enough of a public health matter to have caused the New England Journal of Medicine to release the findings online several weeks before they were to appear in print.
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" (including heart attacks) than a placebo, metformin, or sulfonylurea. The FDA Advisory Committee recommended that label warnings and educational efforts to this effect be instituted immediately. An article by the committee chairman, Dr. Clifford J. Rosen, called "The Rosiglitazone Story -- Lessons from an FDA Advisory Committee Meeting" appeared in the August 30, 2007 issue of The New England Journal of Medicine.
On September 11, 2007, a research found diabetes drug Actos (by Takeda Pharmaceutical Co.) cuts the risk of heart attack, stroke and death, but raises the risk of heart failure, while rival Avandia (by GlaxoSmithKline) raises heart risks.[8]
See also
- Peroxisome proliferator-activated receptor
- Thiazolidinedione, the class of drugs to which rosiglitazone belongs
References
- ↑ Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P (2004). "Evidence for a potent antiinflammatory effect of rosiglitazone". J Clin Endocrinol Metab. 89 (6): 2728–35. PMID 15181049.
- ↑ Risner ME; et al. (2006). "Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease". The Pharmacogenomics Jounal. 6: 246–254.
- ↑ Cobitz, Alexander R (February 2007). Template:PDFlink. GlaxoSmithKline. Retrieved on 2007-04-10.
- ↑ Kahn S, Haffner S, Heise M, Herman W, Holman R, Jones N, Kravitz B, Lachin J, O'Neill M, Zinman B, Viberti G (2006). "Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy". N Engl J Med. 355 (23): 2427–43. PMID 17145742.
- ↑ Nissen SE, Wolski K (2007). "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes". N Engl J Med. doi:10.1056/NEJMoa072761. Free full text with registration
- ↑ Associated Press (May 21 2007). "Diabetes drug linked to heart attacks, death". MSNBC. Retrieved 2007-05-21. Check date values in:
|date=(help) - ↑ FDA (May 21 2007). "FDA Issues Safety Alert on Avandia". Check date values in:
|date=(help) - ↑ Reuters, Study shows risks persist with Glaxo's Avandia
External links
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- Thiazolidinediones
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