出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/10/30 00:28:10」(JST)[Wiki en表示]
|Systematic (IUPAC) name|
|Licence data||EMA:, US FDA:|
|Pregnancy cat.||B3 (AU) C (US)|
|Legal status||POM (UK) ℞-only (US)|
|Excretion||Renal (64%) and fecal (23%)|
|Mol. mass||357.428 g/mol|
| N (what is this?)
Rosiglitazone is an antidiabetic drug in the thiazolidinedione class of drugs. It works as an insulin sensitizer, by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin. It is marketed by the pharmaceutical company GlaxoSmithKline (GSK) as a stand-alone drug (Avandia) and in combination with metformin (Avandamet) or with glimepiride (Avandaryl). Annual sales peaked at approximately $2.5bn in 2006, but declined after reports of adverse effects. The drug's patent expires in 2012.
Some reports have found rosiglitazone is associated with an increased risk of heart attacks, but other reports have not found a statistically significant increase. Concern about adverse effects has reduced the use of rosiglitazone despite its sustained effects on glycemic control. The drug is currently the subject of over 13,000 lawsuits against GSK.[dead link] As of July 2010, GSK has agreed to settlements on more than 11,500 of these suits.
The drug is controversial in the U.S. Some reviewers have concluded rosiglitazone caused more deaths than pioglitazone (Actos), and have recommended rosiglitazone be taken off the market, but an Food and Drug Administration panel disagreed, and it remains on the market in the U.S., subject to significant restrictions. From November 18, 2011, the federal government will not allow Avandia to be sold without a prescription from certified doctors. Patients will be required to be informed of the risks associated with its use, and the drug will be required to be purchased by mail order through specified pharmacies.
In Europe, the European Medicines Agency (EMA) recommended in September 2010 that the drug be suspended from the European market. However, patients currently taking rosiglitazone are advised to discuss alternative options during their next physician appointment. In New Zealand, rosiglitazone was withdrawn from the market in April 2011.
Rosiglitazone is a member of the thiazolidinedione class of drugs. Thiazolidinediones act as insulin sensitizers. They reduce glucose, fatty acid, and insulin blood concentrations. They work by binding to the peroxisome proliferator-activated receptors (PPARs). PPARs are receptors on the membrane of the cell nucleus. Thiazolidinediones enter the cell, bind to the nuclear receptors, and affect the expression of DNA. The several PPARs include PPARα, PPARβ/δ, and PPARγ. Thiazolidinediones bind to PPARγ.
PPARs are expressed in fat cells, cells of the liver, muscle, heart, and inner wall (endothelium) and smooth muscle of blood vessels. PPARγ is expressed mainly in fat tissue, where it regulates genes involved in fat cell (adipocyte) differentiation, fatty acid uptake and storage, and glucose uptake. It is also found in pancreatic beta cells, vascular endothelium, and macrophages. Rosiglitazone is a selective ligand of PPARγ and has no PPARα-binding action. Other drugs bind to PPARα.
Rosiglitazone also appears to have an anti-inflammatory effect in addition to its effect on insulin resistance. Nuclear factor kappa-B (NF-κB), a signaling molecule, stimulates the inflammatory pathways. NF-κB inhibitor (IκB) downregulates the inflammatory pathways. When patients take rosiglitazone, NF-κB levels fall and IκB levels increase.
Rosiglitazone may also benefit patients with Alzheimer's disease who do not express the ApoE4 allele. This is the subject of a clinical trial currently underway.
Rosiglitazone may also treat mild to moderate ulcerative colitis, due to its anti-inflammatory properties as a PPAR ligand.
A clinical trial has suggested these agents may be of use in treating malaria.
Some studies concluded rosiglitazone increases fatalities from heart disease, but other studies do not.
A study in 2007 has been widely cited as finding Avandia may increase the risk of heart attack by as much as 43%.
A meta-analysis in May 2007 reported the use of rosiglitazone was associated with a significantly increased risk of heart attack (odds ratio = 1.43, 95% confidence interval, 1.03 to 1.98; P=0.03), and an even higher risk of death from all cardiovascular diseases (odds ratio = 1.64). The U.S. Food and Drug Administration (FDA) issued an alert on May 21, 2007. On July 30, 2007, an Advisory Committee of the Food and Drug Administration concluded 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, but data from several long term, prospective clinical trials showed when rosiglitazone was compared to metformin, or sulfonylurea, there was no difference in the risk of heart attack. These data, coupled with the meta-analysis, prompted the FDA to state the data on the association between rosiglitazone and myocardial ischemia were inconclusive. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate this, and several other reports have failed to conclude the controversy. Graham argued rosiglitazone caused 500 more heart attacks and 300 more heart failures than its main competitor.
At the same time, a report by the Senate Finance Committee accused GlaxoSmithKline of knowing about the drug's risks well before they became public. The report also criticized the FDA for letting clinical trials continue, despite 83,000 heart attacks from 1999 to 2007 that the FDA linked to rosiglitazone. This Senate Committee report from November 2007 is entitled "The Intimidation of Dr. John Buse and the Diabetes Drug Avandia". The title refers to (temporarily successful) efforts made by GSK beginning in 1999 to intimidate an academic scientist from continuing to suggest Avandia had cardiovascular risk. The drug now bears a black box warning about exactly this risk. Further efforts by the vendors to protect their product are also described at Senate.gov, searchbox "Avandia". GlaxoSmithKline maintains the drug is safe and the Senate report did not consider scientific evidence or the company's efforts to make known its concerns to the parties involved. However, the FDA still recommends patients continue taking it unless their doctors tell them otherwise.
The 2009 RECORD study, an open-label trial published in the Lancet, found no increase in cardiovascular hospitalisation or death with rosiglitazone compared to metformin plus sulfonylurea, but the rate of heart failure causing admission to a hospital or death was significantly increased.
In February 2010, David Graham, the FDA's associate director of drug safety, recommended rosiglitazone be taken off the market. In June 2010, Graham et al., published a retrospective study of 227,571 elderly American patients, comparing roziglitazone to pioglitazone, the other thiazolidinedione marketed in the United States. The authors concluded rosiglitazone was associated with "an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older". The number needed to harm with roziglitazone was sixty.
Both TZDs are contraindicated in patients with NYHA Class III and IV heart failure.
The controversy over adverse effects has dramatically reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control. No studies have shown that rosiglitazone reduces the risk of stroke, amputation, heart attack, blindness, neuropathy or renal failure.
A meta-analysis of observational studies released in March, 2011, provides more evidence that rosiglitazone is associated with a higher risk of heart failure, myocardial infarction and death than a similar agent, pioglitazone. The meta-analysis had 16 observational studies involving 810 000 patients taking rosiglitazone or pioglitazone.
Avandia has been linked to stroke. In a study led by FDA scientist David J. Graham, MD, MPH, by comparing the patient records of elderly patients using Avandia and alternative drug Actos, found Avandia increased the risk of stroke by over 27%.
GlaxoSmithKline reported a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide. The information was based on data from the ADOPT trial. The same increase has been found with pioglitazone (Actos), another TZD.
Both rosiglitazone and pioglitazone have been suspected of causing macular edema, which damages the retina of the eye and causes partial blindness. Blindness is also a possible effect of diabetes, which rosiglitazone is intended to treat. One report documented several occurrences and recommended discontinuation at the first sign of vision problems.
Moderate to severe acute hepatitis has occurred in several adults who had been taking the drug at the recommended dose for two to four weeks. Plasma rosiglitazone concentrations may be significantly increased in patients with pre-existing hepatic impairment.
Rosiglitazone decreases the effectiveness of oral contraceptives.[medical citation needed]
Society and culture
US sales of the drug were of $2.2 billion in 2006. Sales in 2Q 2007 down 22% compared to 2006. 4Q 2007 sales down to $252 million.
Though sales have gone down since 2007 due to safety concerns, Avandia sales for 2009 totalled $1.2 billion worldwide.
The Guardian reported lawsuits over the drug could total from $1 billion to $6 billion, based on research by analysts for UBS, who say 13,000 suits have been filed. Included among those suing: Santa Clara County, California, which claims to have spent $2 million on rosiglitazone between 1999 and 2007 at its public hospital and is asking for "triple damages". In May 2010, GlaxoSmithKline (GSK) reached settlement agreements for some of the cases against the company, agreeing to pay $60 million to resolve 700 suits. In July 2010, GSK reached settlement agreements to close another 10,000 of the lawsuits against it, agreeing to pay about $460 million to settle these suits. In a statement, Michael Miller, the attorney representing 1,500 patients in the suit, said about the settlement, "It's a compromise that allows both sides to put this behind them and move on."
The drug has been under investigation in the US and in Europe. In September 2010, the U.S. Food and Drug Administration (FDA) decided rosiglitazone can remain available, but with certain restrictions. Also, the European Medicines Agency has decided to stop making all rosiglitazone-containing antidiabetes medication available in Europe. The FDA has decided on revising its prescribing information and medication guides for all rosilitazone containing medicines. The US label for rosiglitazone (Avandia, GlaxoSmithKline) and all rosiglitazone-containing medications (Avandamet and Avandaryl) now include the additional safety information and restrictions. The revised labels restrict use to patients already taking a rosiglitazone-containing medicine or to new patients who are unable to achieve adequate glycemic control on other diabetes medications and to those, who in consultation with their healthcare provider, have decided not to take Actos (pioglitazone) or other pioglitazone-containing medicines for medical reasons.
United States investigations
The FDA began investigating the drug in 2007 after reports it likely caused an increased risk in heart attacks, but following a 2007 study, an FDA advisory panel agreed Avandia did not cause a statistically significant increase in heart attacks. The FDA voted to keep the drug on the market; a few months later, however, the agency added a black-box warning about potential heart risks of Avandia. A study was conducted evaluating the geographic variation in the use of rosiglitazone following the black box warning issued in 2007. Residual use varied by state, which may be explained by uncertainty regarding how to translate FDA warnings into practice, by differences in coverage policies among health plans and in formularies among states, and by regional differences in the distribution and influence of pharmaceutical marketing, specialists, and opinion leaders.
In 2007, a panel of independent researchers reported Avandia could, in fact, increase patients' risks of heart attack, but they recommended it remain on the market. An FDA oversight committee voted in 2007, eight to seven, to accept that advice and keep it on the market.
GlaxoSmithKline is currently being investigated by the FDA and the US Congress regarding Avandia.
Senators Democrat Max Baucus and Republican Charles Grassley filed a report urging GSK to withdraw Avandia in 2008 due to the side effects. The report noted the drug caused 500 avoidable heart attacks a month, and Glaxo officials sought to intimidate doctors who criticized the drug. It also said GSK continued to sell and promote the drug despite knowing the increased risk of heart attacks and stroke.
The Senate Finance Committee, in a panel investigation, revealed emails from GSK company officials that suggest the company downplayed scientific findings about safety risks dating back to 2000. It was also alleged by the committee that the company initiated a "ghostwriting campaign", whereby GSK sought outside companies to write positive articles about Avandia to submit to medical journals. GSK defended itself by presenting data that its own tests found Avandia to be safe, although an FDA staff report showed the conclusions were flawed. Many studies have found the drug to have serious safety concerns.
On July 14, 2010, after two days of extensive deliberations, the FDA panel investigating Avandia came to a mixed vote. Twelve members of the panel voted to take the drug off the market, 17 recommended to leave it on but with a more revised warning label, and three voted to keep it on the market with the current warning label. The panel has come to some controversy, however; on July 20, 2010, one of the panelists was discovered to have been a paid speaker for GlaxoSmithKline, arrousing questions of a conflict of interest. This panel member was one of the three who voted to keep Avandia on the market with no additional warning labels. The FDA is expected to vote soon on what to do next in regards to Avandia, though the FDA almost always agrees with its panel votes.
In 2012, the U.S. Justice Department announced GlaxoSmithKline had agreed to plead guilty and pay a $3 billion fine, in part for withholding the results of two studies of the cardiovascular safety of Avandia between 2001 and 2007.
According to a probe by the British Medical Journal in September 2010, the United Kingdom's Commission on Human Medicines recommended to the Medicines and Healthcare Products Regulatory Agency (MHRA) back in July 2010, to withdraw Avandia sale because its "risks outweigh its benefits". Additionally, the probe revealed that in 2000, members of the European panel in charge of reviewing Avandia prior to its approval had concerns about the long-term risks of the drug. The European Medicines Agency recommended on 23 September 2010 that Avandia be suspended from the European market.
Rosiglitazone was withdrawn from the New Zealand market April 2011 because Medsafe concluded the suspected cardiovascular risks of the medicine for patients with type 2 diabetes outweigh its benefits.
Controversy and response
Following the reports in 2007 that Avandia can significantly increase the risk of heart attacks, the drug has been controversial. A 2010 article in Time uses the Avandia case as evidence of a broken FDA regulatory system that "may prove criminal as well as fatal". It details the disclosure failures, adding, "Congressional reports revealed that GSK sat on early evidence of the heart risks of its drug, and that the FDA knew of the dangers months before it informed the public." It reports, "the FDA is investigating whether GSK broke the law by failing to fully inform the agency of Avandia's heart risks", according to deputy FDA commissioner Dr. Joshua Sharfstein. GSK threatened academics who reported adverse research results, and received multiple warning letters from the FDA for deceptive marketing and failure to report clinical data.
The maker of the drug, GlaxoSmithKline, has dealt with serious backlash against the company for the drug's controversy. Sales on the drug dropped significantly after the story first broke in 2007, dropping from $2.5 billion in 2006 to less than $408 million in 2009 in the US.
In response to the rise in risk of heart attacks, the Indian government ordered GSK to suspend its research study, called TIDE, in 2010. Takeda Pharmaceuticals responded to the controversy by running a large advertising campaign for its rival diabetes drug Actos, first in 2007 and again in 2010. The FDA also halted the TIDE study in the United States.
Three doctors' groups, the Endocrine Society, the American Diabetes Association and the American Association of Clinical Endocrinologists, urged patients to continue to take the drug as it would be much worse to stop all treatment, despite any associated risk, but that patients could consult their doctors and begin a switch to a different drug if they or their doctors find concern. The American Heart Association said in a statement in June 2010: " ...the reports deserves serious consideration, and patients with diabetes who are 65 years of age or older and being treated with rosiglitazone should discuss the findings with their prescribing physician....". "For patients with diabetes, the most serious consequences are heart disease and stroke, and the risk of suffering from them is significantly increased when diabetes is present. As in most situations, patients should not change or stop medications without consulting their healthcare provider."
In Nov 2011, in a unique case, all sales of rosiglitazone were directed by the U.S. Department of Health and Human Services to go through Liberty Medical in Port St. Lucie, Florida. As a result of this action, the price of the drug immediately more than doubled, and in some cases, increased 250%.
- US 5002953
- Ajjan RA, Grant PJ (2008). "The cardiovascular safety of rosiglitazone". Expert Opin Drug Saf 7 (4): 367–76. doi:10.1517/147403126.96.36.1997. PMID 18613801.
- Gardiner Harris (February 19, 2010). "Controversial Diabetes Drug Harms Heart, U.S. Concludes". New York Times. http://www.nytimes.com/2010/02/20/health/policy/20avandia.html.
- "Most Popular E-mail Newsletter". USA Today. 2011-05-24. http://yourlife.usatoday.com/health/medical/heartdisease/story/2011/05/Diabetes-drug-Avandia-to-be-pulled-from-retail-shelves/47316450/1?csp=34news&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+usatoday-NewsTopStories+%28News+-+Top+Stories%29.
- European Medicines Agency recommends suspension of Avandia, Avandamet and Avaglim
- Call to 'suspend' diabetes drug
- "Diabetes drug withdrawn". Stuff.co.nz. NZPA. 17 February 2011. http://www.stuff.co.nz/4669573. Retrieved 5 November 2011.
- Thiazolidinediones, Hannele Yki-Järvinen, New Engl J Med 351:1106-1118 (September 9, 2004).
- 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. doi:10.1210/jc.2003-032103. PMID 15181049.
- Risner ME et al.; Saunders, A M; Altman, J F B; Ormandy, G C; Craft, S; Foley, I M; Zvartau-Hind, M E; Hosford, D A et al. (2006). "Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease". The Pharmacogenomics Journal 6 (4): 246–254. doi:10.1038/sj.tpj.6500369. PMID 16446752.
- Lewis JD, Lichtenstein GR, Deren JJ, et al. (2008). "Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo Controlled Trials". Gastroenterology 134 (5): 688–695. doi:10.1053/j.gastro.2008.03.030. PMID 18471502.
- Boggild AK, Krudsood S, Patel SN, Serghides L, Tangpukdee N, Katz K, Wilairatana P, Liles WC, Looareesuwan S, Kain KC (2009). "Use of Peroxisome proliferator-activated receptor gamma agonists as adjunctive treatment for Plasmodium falciparum malaria: A randomized, double-blind, placebo-controlled trial". Clin. Infect. Dis. 49 (6): 841–9. doi:10.1086/605431. PMID 19673614.
- LA Times Avandia: When does a drug's harm outweigh its benefit? by David Lazarus. 1 July 2010. Access date: July 24, 2010
- Nissen SE, Wolski K (2007). "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes". N Engl J Med 356 (24): 2457–71. doi:10.1056/NEJMoa072761. PMID 17517853. http://content.nejm.org/cgi/content/full/356/24/2457. Lay summary – Associated Press (2007-05-21).
- U.S. Food and Drug Administration (May 21, 2007). "FDA Issues Safety Alert on Avandia". http://www.fda.gov/bbs/topics/NEWS/2007/NEW01636.html.
- "Diabetes Drug Avandia Targeted By Reviewers on Safety". ABC News. 2010-02-23. http://abcnews.go.com/GMA/OnCall/diabetes-drug-avandia-targeted-fda-reviewers-safety/story?id=9914308.
- Ranii, David (2010-02-23). "Avandia fallout could hit Triangle". News & Observer. http://www.newsobserver.com/2010/02/23/353164/avandia-fallout-could-hit-triangle.html?storylink=misearch. Retrieved 2010-03-05.
- Home PD, Pocock SJ, Beck-Nielsen H et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. The Lancet. In Press, Corrected Proof. Available at: http://www.sciencedirect.com/science/article/B6T1B-4WGD87Y-1/2/0efabb7eba7ca1f4f7c556bd636e19ab.
- Graham, D.J. et al.: Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone. JAMA. 2010;304(4): doi:10.1001/jama.2010.920 Full text
- Hughes, Sue (27 March 2011). "More damning data on rosiglitazone". theheart.org. http://www.theheart.org/article/1199863.do. Retrieved 6 April 2011.
- Freeman, David W (2010-06-29). "Diabetes Drug and Risk: Avandia Linked to Stroke, Heart Trouble, Deaths". CBS News. http://www.cbsnews.com/8301-504763_162-20009124-10391704.html.
- Elizabeth Agnvall (2010-06-28). "Drug Safety: Diabetes Drug Found to Increase Risk of Stroke, Heart Attack and Death. Researchers question why Avandia has not been removed from the market". AARP Bulletin. http://www.aarp.org/health/drugs-supplements/info-06-2010/diabetes_drug_found_to_increase_risk_of_stroke_heart_failure_and_death.html. Retrieved 2011-11-03.
- Daniel J. DeNoon (2010-06-28). "New Study: Avandia Riskier Than Actos: More Deaths, Heart Failure, Strokes in Elderly Patients Taking Diabetes Drug Avandia vs. Actos". WebMD Health News. http://diabetes.webmd.com/news/20100628/new-study-avandia-riskier-than-actos.
- Cobitz, Alexander R (February 2007). PDF (49.9 KiB). GlaxoSmithKline. Retrieved on 10 April 2007.
- 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. doi:10.1056/NEJMoa066224. PMID 17145742.
- R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1399-1400.
- Rubin, Rita (2007-07-26). "FDA panels to weigh Avandia heart risks". USA Today. http://www.usatoday.com/news/health/2007-07-25-avandia-fda_N.htm. Retrieved 2010-05-22.
- "Glaxo Fourth-Quarter Profit Fell 10% on Avandia Sales (Update6)". Bloomberg. 2008-02-07. http://www.bloomberg.com/apps/news?pid=20601087&sid=aHobgoX8jyfg&refer=home.
- Ranii, David (2010-03-05). "Avandia could cost GSK billions". News & Observer. http://www.newsobserver.com/2010/03/05/371760/avandia-could-cost-gsk-billions.html?storylink=misearch. Retrieved 2010-03-05.
- Ranii, David (2010-03-01). "California county sues Glaxo over diabetes drug". News & Observer. http://www.newsobserver.com/2010/03/01/365150/california-county-sues-glaxo-over.html?storylink=misearch. Retrieved 2010-03-05. [dead link]
- Feeley, Jef; Kelley, Trista (2010-05-11). "Glaxo Said to Pay About $60 Million in First Avandia Heart-Risk Settlement". Bloomberg. http://www.bloomberg.com/news/2010-05-10/glaxo-said-to-pay-about-60-million-in-first-settlement-of-avandia-drug.html.
- Feeley, Jef; Kelley, Trista (2010-07-13). "Glaxo Said to Pay $460 Million to Settle Avandia Damage Suits". Bloomberg. http://noir.bloomberg.com/apps/news?pid=newsarchive&sid=aP.inHBfGVcU.
- Dawber, Alistair (2010-07-14). "GSK 'settles Avandia claims' on first day of safety hearing". The Independent (London). http://www.independent.co.uk/news/business/news/gsk-settles-avandia-claims-on-first-day-of-safety-hearing-2025957.html.
- Wood, Shelley. "FDA restricts rosiglitazone; EMA pulls the plug". http://www.theheart.org. http://www.theheart.org/article/1125181.do. Retrieved 1 April 2011.
- O'Riordan, Michael. "New rosiglitazone label includes restrictions on use". http://www.theheart.org. http://www.theheart.org/article/1182011.do. Retrieved 1 April 2011.
- "GSK revises US Avandia label to include new restrictions on use". http://www.gsk.com. http://www.gsk.com/media/pressreleases/2011/2011_pressrelease_10024.htm. Retrieved 1 April 2011.
- Shah, Nilay; Victor M Montori, Harlan M Krumholz, Karen Tu, G Caleb Alexander and Cynthia A Jackevicius (25). "Responding to an FDA Warning — Geographic Variation in the Use of Rosiglitazone". New England Journal of Medicine 363 (22): 2081–2084. doi:10.1056/NEJMp1011042. PMID 21083379.
- Lazarus, David (2010-07-01). "Avandia: When does a drug's harm outweigh its benefit?". The Los Angeles Times. http://articles.latimes.com/2010/jul/01/business/la-fi-lazarus-20100702.
- Mundy, Alicia (2010-07-20). "Panelist Who Backed Avandia Gets Fees From Glaxo". The Wall Street Journal. http://online.wsj.com/article/SB10001424052748704720004575377552600421936.html.
- Gallagher, James (2010-07-20). "Report: Avandia panelist paid by GSK". http://triangle.bizjournals.com/triangle/stories/2010/07/19/daily18.html.
- "Glaxo Agrees to Pay $3 Billion in Fraud Settlement". The New York Times. July 2, 2012. http://www.nytimes.com/2012/07/03/business/glaxosmithkline-agrees-to-pay-3-billion-in-fraud-settlement.html.
- Douglas, Jason (2010-09-06). "U.K. Medical Journal Questions Avandia License". The Wall Street Journal. http://online.wsj.com/article/SB10001424052748703713504575475884140520538.html?mod=googlenews_wsj.
- "Diabetes drug to be withdrawn over heart risk fears". New Zealand Herald. Feb 17, 2011. http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10706910.
- After Avandia: Does the FDA Have a Drug Problem? Time, Thursday, Aug. 12, 2010, http://www.time.com/time/health/article/0,8599,2010028,00.html
- "Don't dump Avandia, diabetes groups urge patients". Reuters. 2010-07-15. http://www.reuters.com/article/idUSN1521260120100715.
- Maugh II, Thomas H. (2010-07-15). "Patients taking Avandia should keep on doing so, doctor groups say". The Los Angeles Times. http://articles.latimes.com/2010/jul/15/news/la-heb-avandia-20100715.
- Katz, Neil (2010-07-16). "Avandia News: What You Need to Know". CBS News. http://www.cbsnews.com/8301-504763_162-20010767-10391704.html.
- "Booster Shots". The Los Angeles Times. 2010-06-29. http://latimesblogs.latimes.com/booster_shots/2010/06/avandia-rosiglitazone-heart-attack.html.
- Rosiglitazone bound to proteins in the PDB: S-rosiglitazone, R-rosiglitazone
- Official website
- MedlinePlus article
- ClinicalTrials.gov NCT00265148 Brain Imaging Study of Rosiglitazone Efficacy and Safety in Alzheimer's Disease
- U.S. National Library of Medicine: Drug Information Portal - Rosiglitazone
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. 糖尿病の治療におけるチアゾリジン thiazolidinediones in the treatment of diabetes mellitus
- 2. 2型糖尿病の治療のためのジペプチジルペプチダーゼ4（DPP-4）阻害剤 dipeptidyl peptidase 4 dpp 4 inhibitors for the treatment of type 2 diabetes mellitus
- 3. 2型糖尿病の予防 prevention of type 2 diabetes mellitus
- 4. 糖尿病における心不全 heart failure in diabetes mellitus
- 5. 成人の2型糖尿病における血糖の初期マネージメント initial management of blood glucose in adults with type 2 diabetes mellitus
- An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment.
- Xu Y1, Romero R2, Miller D1, Kadam L3, Mial TN4, Plazyo O1, Garcia-Flores V4, Hassan SS4, Xu Z4, Tarca AL4, Drewlo S3, Gomez-Lopez N5.
- Journal of immunology (Baltimore, Md. : 1950).J Immunol.2016 Mar 15;196(6):2476-91. doi: 10.4049/jimmunol.1502055. Epub 2016 Feb 17.
- Decidual macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo a proinflammatory (M1) polarization during spontaneous preterm labor and that PPARγ ac
- PMID 26889045
- Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors.
- Taub M1.
- Biochemical and biophysical research communications.Biochem Biophys Res Commun.2016 Mar 11;471(3):342-7. doi: 10.1016/j.bbrc.2016.02.018. Epub 2016 Feb 8.
- Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10(-5) M) in order to elicit growth inhibitory effects. In this report, when employing lower concen
- PMID 26869517
- Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats.
- Zhou J1, Du X2, Long M1, Zhang Z1, Zhou S1, Zhou J3, Qian G4.
- European journal of pharmacology.Eur J Pharmacol.2016 Mar 5;774:87-94. doi: 10.1016/j.ejphar.2016.02.007. Epub 2016 Feb 3.
- The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by s
- PMID 26849937
- Rosiglitazone comes as a tablet to take by mouth. It is usually taken once or twice daily with or without meals. Take rosiglitazone at about the same time(s) every day. Follow the directions on your prescription label ...
- Sigma-Aldrich offers Sigma-R2408, Rosiglitazone for your research needs. Find product specific information including CAS, MSDS, protocols and references. ... Packaging 10, 50 mg in glass bottle Biochem/physiol Actions ...