| 词条 | Pioglitazone |
| 释义 |
| Watchedfields = changed | verifiedrevid = 464207213 | IUPAC_name = (RS)-5-(4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl)thiazolidine-2,4-dione | image = Pioglitazone.svg | width = 271 | chirality = Racemic mixture | image2 = Pioglitazone ball-and-stick model.png | tradename = Actos, others | Drugs.com = {{drugs.com|monograph|pioglitazone-hydrochloride}} | MedlinePlus = a699016 | licence_EU = yes | licence_US = Actos | pregnancy_category = C | legal_UK = POM | legal_US = Rx-only | routes_of_administration = By mouth | class = Thiazolidinedione | protein_bound = >99% | metabolism = liver (CYP2C8) | elimination_half-life = 3–7 hours | excretion = in bile | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 111025-46-8 | ATC_prefix = A10 | ATC_suffix = BG03 | PubChem = 4829 | IUPHAR_ligand = 2694 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01132 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 4663 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = X4OV71U42S | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08378 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 8228 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 595 | C=19 | H=20 | N=2 | O=3 | S=1 | molecular_weight = 356.44 g/mol | smiles = O=C1NC(=O)SC1Cc3ccc(OCCc2ncc(cc2)CC)cc3 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C19H20N2O3S/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = HYAFETHFCAUJAY-UHFFFAOYSA-N | melting_point = 183 | melting_high = 184 }}Pioglitazone, sold under the brand name Actos among others, is a medication used to treat diabetes mellitus type 2.[1] It may be used with metformin, a sulfonylurea, or insulin.[1] Use is recommended together with exercise and diet.[3] It is not recommended in diabetes mellitus type 1.[3] It is taken by mouth.[1] Common side effects include headaches, muscle pains, inflammation of the throat, and swelling.[1] Serious side effects may include bladder cancer, low blood sugar, heart failure, and osteoporosis.[1][1] Use in not recommended in pregnancy or breastfeeding.[2] It is in the thiazolidinedione (TZD) class and works by improving sensitivity of tissues to insulin.[3] Pioglitazone was patented in 1985 and came into medical use in 1999.[4] It is avaliable as a generic medication.[2] A month supply in the United Kingdom costs the NHS less than one £ as of 2019.[2] In the United States the wholesale cost of this amount is about 3.20 USD.[5] In 2016 it was the 116th most prescribed medication in the United States with more than 6 million prescriptions.[6] It was withdrawn in France and Germany in 2011.[7] Medical usesPioglitazone is used to lower blood glucose levels in diabetes mellitus type 2 (T2DM) either alone or in combination with a sulfonylurea, metformin, or insulin.[8] While pioglitazone does decrease blood sugar levels, the main study that looked at the medication found no difference in the main cardiovascular outcomes that were looked at.[9] The secondary outcome of death from all causes, myocardial infarction, and stroke were lower.[9] ContraindicationsPioglitazone 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.[10] 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. Pioglitazone and all other drugs of its class (thiazolidinediones) are absolutely contraindicated in patients with heart failure.[10] Side effectsA 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. The information was based on data from the ADOPT trial. Following release of this statement, Takeda Pharmaceutical Company, the developer of pioglitazone (sold as Actos in many markets) admitted that it has similar implications for female patients.[11] The risk of hypoglycemia is low in the absence of other drugs that lower blood glucose. 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 an increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems. Chronic administration of the drug has led to occasional instances of cholestatic hepatitis, reversible upon drug discontinuation.[12] 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" when compared to placebo, but when compared to other diabetes drugs, there was no increased risk. Pioglitazone is currently being reviewed. A meta-analysis released subsequently showed that pioglitazone reduced the risk of ischemic cardiac events rather than increased the risk, but increased CHF.[13] Bladder cancerOn June 9, 2011 the French Agency for the Safety of Health Products decided to withdraw pioglitazone due to high risk of bladder cancer.[14] This suspension was based on the results of an epidemiological study conducted by the French National Health Insurance. According to the results of the epidemiological study, the French agency found that patients, who were taking Actos for a long time to aid in type 2 diabetes mellitus, significantly increased risk of bladder cancer compared with patients who were taking other diabetes medications.[15] On June 10, 2011 Germany's Federal Institute for Drugs and Medical Devices also advised doctors not to prescribe the medication until further investigation of the cancer risk had been conducted.[16] On June 15, 2011 the U.S. FDA announced that pioglitazone use for more than one year may be associated with an increased risk of bladder cancer, and two months later the label was updated with an additional warning about this risk.[17] A 2017 meta-analysis of diabetes found no difference in the rates of bladder cancer attributed to the pioglitazone.[18] Drug interactions{{Unreferenced section|date=March 2011}}Combination with sulfonylureas or insulin reciprocally exponentiate risk of hypoglycemia. Therapy with pioglitazone increase the chance of pregnancy in individuals taking oral contraception. Mechanism of actionPioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α.[19][20] It modulates the transcription of the genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues, decreases gluconeogenesis in the liver, and reduces quantity of glucose and glycated hemoglobin in the bloodstream. 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.[21][22] Society and cultureIn 2008 it generated the tenth-highest amount of money for a medication in the U.S. in 2008, with sales exceeding $2.4 billion.[23] Brand namesPioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe, Glizone and Pioz in India by Zydus Cadila and USV Limited, respectively and Zactos in Mexico by Takeda Pharmaceuticals. On August 17, 2012 the US FDA announced its approval of the first generic version of Actos.[24] ResearchThere is tentative research that suggests that pioglitazone may be useful for treating major depression.[25] Because it is thought to reduce glial cell activity, it was studied in a small clinical treat in children with autism, under the autoimmune/inflammatory hypotheses of the cause of autism.[26] References1. ^1 2 3 4 {{cite web |title=Pioglitazone Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/pioglitazone-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |accessdate=3 March 2019 |language=en}} 2. ^1 2 3 4 5 {{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=694|edition=76}} 3. ^{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=694|edition=76}} 4. ^{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=450 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA450 |language=en}} 5. ^{{cite web |title=NADAC as of 2019-02-27 |url=https://data.medicaid.gov/Drug-Pricing-and-Payment/NADAC-as-of-2019-02-27/s7c9-pfa6 |website=Centers for Medicare and Medicaid Services |accessdate=3 March 2019 |language=en}} 6. ^{{cite web |title=The Top 300 of 2019 |url=https://clincalc.com/DrugStats/Top300Drugs.aspx |website=clincalc.com |accessdate=22 December 2018}} 7. ^{{cite book |last1=Burant |first1=Charles |title=Medical Management of Type 2 Diabetes |date=2012 |publisher=American Diabetes Association |isbn=9781580404570 |page=63 |url=https://books.google.ca/books?id=b4osDQAAQBAJ&pg=PA63 |language=en}} 8. ^{{cite web | title = ACTOS (pioglitazone) Prescribing Information | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021073s046lbl.pdf | publisher = United States Food and Drug Administration | date = November 2013}} 9. ^1 {{cite journal | vauthors = Scheen AJ | title = Outcomes and lessons from the PROactive study | journal = Diabetes Research and Clinical Practice | volume = 98 | issue = 2 | pages = 175–86 | date = November 2012 | pmid = 23020930 | doi = 10.1016/j.diabres.2012.09.001 | quote = Since 2005, there has been much debate on the relative value of the statistically non-significant 10% reduction in the quite challenging primary composite endpoint (combining cardiovascular disease-driven and procedural events in all vascular beds) versus the statistically significant 16% decrease in the more robust and conventional main secondary endpoint (all-cause mortality, myocardial infarction, and stroke) observed with pioglitazone. }} 10. ^1 {{cite web |url=http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=22567#_CONTRAINDICATIONS |title=ACTOS (pioglitazone hydrochloride) tablet |author=U.S. National Library of Medicine |year=2010 |website= |publisher=National Institutes of Health |access-date=24 December 2012}} 11. ^{{cite web | url = http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM153896.pdf | title = Observation of an Increased Incidence of Fractures in Female Patients Who Received Long-Term Treatment with ACTOSO (pioglitazone HOI) Tablets for Type 2 Diabetes Mellitus | access-date = 2012-04-04 | last = Takeda | date = March 2007 }} 12. ^{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1271–1272 }} 13. ^{{cite journal | vauthors = Lincoff AM, Wolski K, Nicholls SJ, Nissen SE | title = Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials | journal = JAMA | volume = 298 | issue = 10 | pages = 1180–8 | date = September 2007 | pmid = 17848652 | doi = 10.1001/jama.298.10.1180 }} 14. ^{{cite web | title = L'antidiabétique Actos retiré du marché | trans-title = Actos antidiabetic withdrawn from the market | language = French | url = http://www.lefigaro.fr/flash-actu/2011/06/09/97001-20110609FILWWW00505-info-le-figaro-lantidiabetique-actos-retire-du-marche.php | work = Le Figaro | date = 9 June 2011 }} 15. ^{{cite web | first = Imtiaz Ibne | last = Alam | name-list-format = vanc | date = 1 January 2012 | url = http://www.medical-reference.net/2011/12/france-and-germany-suspended-use-of.html | title = France and Germany Suspended Use of Actos for Bladder Cancer Risk | work = Medical-Reference }} 16. ^{{cite news| url=https://www.reuters.com/article/2011/06/10/takeda-germany-idUSL3E7HA0X920110610 | work=Reuters | first=James | last=Topham | title=UPDATE 2-Germany joins France in suspending top Takeda drug | date=June 10, 2011}} 17. ^{{cite web | title = FDA Drug Safety Communication: Updated drug labels for pioglitazone-containing medicines | date = 4 August 2011 | url = http://www.fda.gov/Drugs/DrugSafety/ucm266555.htm | publisher = United States Food and Drug Administration }} 18. ^{{cite journal | vauthors = Filipova E, Uzunova K, Kalinov K, Vekov T | title = Pioglitazone and the Risk of Bladder Cancer: A Meta-Analysis | journal = Diabetes Therapy | volume = 8 | issue = 4 | pages = 705–726 | date = August 2017 | pmid = 28623552 | pmc = 5544610 | doi = 10.1007/s13300-017-0273-4 }} 19. ^{{cite journal | vauthors = Gillies PS, Dunn CJ | title = Pioglitazone | journal = Drugs | volume = 60 | issue = 2 | pages = 333–43; discussion 344–5 | date = August 2000 | pmid = 10983737 | doi = 10.2165/00003495-200060020-00009 }} 20. ^{{cite journal | vauthors = Smith U | title = Pioglitazone: mechanism of action | journal = International Journal of Clinical Practice. Supplement | volume = | issue = 121 | pages = 13–8 | date = September 2001 | pmid = 11594239 | doi = }} 21. ^{{cite journal | vauthors = Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR | title = Identification of a novel mitochondrial protein ("mitoNEET") cross-linked specifically by a thiazolidinedione photoprobe | journal = American Journal of Physiology. Endocrinology and Metabolism | volume = 286 | issue = 2 | pages = E252–60 | date = February 2004 | pmid = 14570702 | doi = 10.1152/ajpendo.00424.2003 | url = http://ajpendo.physiology.org/content/286/2/E252.full.pdf+html }} 22. ^{{cite journal | vauthors = Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA | title = MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 36 | pages = 14342–7 | date = September 2007 | pmid = 17766440 | pmc = 1963346 | doi = 10.1073/pnas.0707189104 }} 23. ^{{cite web | url = http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=ACTOS | title = Details for Actos | work = Drug Patent Watch }} 24. ^{{cite web | title = FDA approves first generic Actos to treat type 2 diabetes | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315951.htm | archive-url = https://web.archive.org/web/20160104163520/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm315951.htm | dead-url = yes | archive-date = 4 January 2016| publisher = United States Food and Drug Administration | date = 17 August 2012}} 25. ^{{cite journal | vauthors = Colle R, de Larminat D, Rotenberg S, Hozer F, Hardy P, Verstuyft C, Fève B, Corruble E | title = Pioglitazone could induce remission in major depression: a meta-analysis | journal = Neuropsychiatric Disease and Treatment | volume = 13 | issue = | pages = 9–16 | year = 2017 | pmid = 28031713 | doi = 10.2147/NDT.S121149 | pmc=5182046}} 26. ^{{cite journal | vauthors = Doyle CA, McDougle CJ | title = Pharmacotherapy to control behavioral symptoms in children with autism | journal = Expert Opinion on Pharmacotherapy | volume = 13 | issue = 11 | pages = 1615–29 | date = August 2012 | pmid = 22550944 | doi = 10.1517/14656566.2012.674110 }} External links
9 : RTT|3β-Hydroxysteroid dehydrogenase inhibitors|Eli Lilly and Company|Takeda Pharmaceutical Company|Phenol ethers|Pyridines|Thiazolidinediones|IARC Group 2A carcinogens|CYP17A1 inhibitors |
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