| 词条 | Dapagliflozin |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 457635935 | IUPAC_name = (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol | image = Dapagliflozin skeletal.svg | width = 275 | image2 = Haworth projection of dapagliflozin.svg | width2 = 225 | caption = Haworth projection (bottom) | pronounce = {{IPAc-en|ˌ|d|æ|p|ə|g|l|ᵻ|ˈ|f|l|oʊ|z|ɪ|n}} {{respell|DAP|ə-glif|LOH|zin}} | tradename = Forxiga, Farxiga | Drugs.com = {{Drugs.com|UK|forxiga-5-mg-10-mg-film-coated-tablets-2402}} | licence_EU = yes | licence_US = Dapagliflozin | pregnancy_AU = | pregnancy_US = C | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = POM | legal_US = Rx-only | legal_status = Rx-only | routes_of_administration = By mouth (tablets) | bioavailability = 78% (after 10 mg dose) | protein_bound = ~91% | metabolism = UGT1A9 (major), CYP (minor) | metabolites = Dapagliflozin 3-O-glucuronide (inactive) | elimination_half-life = ~12.9 hours | excretion = Urine (75%), feces (21%)[1]{{rp|5}} | IUPHAR_ligand = 4594 | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 461432-26-8 | CAS_supplemental = | ATC_prefix = A10 | ATC_suffix = BK01 | ATC_supplemental = | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 429910 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 85078 | PubChem = 9887712 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = DB06292 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 8063384 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 1ULL0QJ8UC | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = D08897 | synonyms = BMS-512148; (1S)-1,5-anhydro-1-C4-chloro-3-[(4-ethoxyphenyl)methyl]phenylD-glucitol | chemical_formula = | C=21 | H=25 | Cl=1 | O=6 | molecular_weight = 408.873 g/mol | smiles = Clc1ccc(cc1Cc2ccc(OCC)cc2)[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = JVHXJTBJCFBINQ-ADAARDCZSA-N }} Dapagliflozin (INN,[2] USAN,[3] trade name Farxiga {{IPAc-en|f|ɑr|ˈ|s|iː|g|ə}} {{respell|far|SEE|gə}} in the U.S. and Forxiga in the EU and Russia) is a drug of the gliflozin class, used to treat type 2 diabetes. It was developed by Bristol-Myers Squibb in partnership with AstraZeneca. Medical usesThe FDA approved dapagliflozin on January 8, 2014 for glycemic control, along with diet and exercise, in adults with type 2 diabetes.[4] SGLT2 inhibitors, including dapagliflozin, reduce the likelihood of hospitalization for congestive heart failure or progression of renal disease in persons with diabetes mellitus type 2 and reduce the likelihood of stroke and heart attack in persons with diabetes mellitus type 2 who have known atherosclerotic vascular disease.[5] In 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion on the drug.[6] It is now marketed in a number of European countries.[7] The FDA approved the combination product dapagliflozin and metformin hydrochloride extended-release, called Xigduo XR, in November 2014.[8] In Feb 2017 the FDA approved a once-daily combination of dapagliflozin 10 mg and saxagliptin 5 mg, as Qtern.[9] Adverse effectsSince dapagliflozin leads to heavy glycosuria (sometimes up to about 70 grams per day) it can lead to rapid weight loss and tiredness. The glucose acts as an osmotic diuretic (this effect is the cause of polyuria in diabetes) which can lead to dehydration. The increased amount of glucose in the urine can also worsen the infections already associated with diabetes, particularly urinary tract infections and thrush (candidiasis). Rarely, use of a SGLT2 drug, including dapagliflozin, is associated with necrotizing fasciitis of the perineum, also called Fournier gangrene.[10] Dapagliflozin is also associated with hypotensive reactions. There are concerns it may increase the risk of diabetic ketoacidosis.[11] Mechanism of actionDapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes blood glucose to be eliminated through the urine.[12] In clinical trials, dapagliflozin lowered HbA1c by 0.6 versus placebo percentage points when added to metformin.[13] SelectivityThe IC50 for SGLT2 is less than one thousandth of the IC50 for SGLT1 (1.1 versus 1390 nmol/L), so that the drug does not interfere with intestinal glucose absorption.[14] ResearchClinical trials to assess effectiveness for patients with type 1 diabetes are underway.[15][16] References1. ^{{cite web|title=Farxiga (dapagliflozin) Tablets, for Oral Use. Full Prescribing Information|url=http://www.azpicentral.com/farxiga/pi_farxiga.pdf|publisher=AstraZeneca Pharmaceuticals|accessdate=15 November 2016}} 2. ^{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 59 | url = http://www.who.int/medicines/publications/druginformation/innlists/RL59.pdf | publisher = World Health Organization | accessdate = 15 November 2016 | page = 50 | date = 2008}} 3. ^{{cite web|title=Statement on a Nonproprietary Name Adopted by the USAN Council |url=http://www.ama-assn.org/ama1/pub/upload/mm/365/dapagliflozin.pdf |publisher=American Medical Association |accessdate=15 November 2016 |archiveurl=https://web.archive.org/web/20120207124414/http://www.ama-assn.org/ama1/pub/upload/mm/365/dapagliflozin.pdf |archivedate=7 February 2012 |deadurl=yes |df= }} 4. ^{{cite news | title = FDA Approves Farxiga to Treat Type 2 Diabetes | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm380829.htm | accessdate = 15 November 2016 | publisher = Food and Drug Administration | date = 8 January 2014}} 5. ^{{cite journal |vauthors=Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, Mosenzon O, Kato ET, Cahn A, ((Furtado RHM)), Bhatt DL, Leiter LA, McGuire DK, ((Wilding JPH)), Sabatine MS |title=SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials |journal=Lancet |volume=393 |issue=10166 |pages=31–39 |date=January 2019 |pmid=30424892 |doi=10.1016/S0140-6736(18)32590-X |url=}} 6. ^{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002322/WC500136025.pdf|title=Forxiga EPAR summary for the public|publisher=European Medicines Agency|date=12 November 2012}} 7. ^Drugs.com: {{Drugs.com|international|forxiga}} for Forxiga. 8. ^{{cite web | title = US FDA Approves Once-Daily Xigduo™ XR Tablets for Adults with Type 2 Diabetes | url = https://www.astrazeneca.com/media-centre/press-releases/2014/us-fda-approved-xigduo-type-2-diabetes-patients-30102014.html | website = www.astrazeneca.com | publisher = AstraZeneca | date = 30 October 2014}} 9. ^ 10. ^https://www.fda.gov/Drugs/DrugSafety/ucm617360.htm 11. ^{{cite web | title = Safety Alerts for Human Medical Products — SGLT2 inhibitors: Drug Safety Communication — FDA Warns Medicines May Result in a Serious Condition of Too Much Acid in the Blood | url = http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm446994.htm | publisher = Food and Drug Administration | accessdate = 15 November 2016 | language = en | date = 15 May 2015}} 12. ^{{cite web|url=http://www.prous.com/molecules/default.asp?ID=165|title=Life Sciences - Clarivate|website=Clarivate}} 13. ^{{cite web|url=http://www.uendocrine.com/217-how-effective-are-sglt2-inhibitors|title=UEndocrine: Internet Endocrinology Community|website=uendocrine.com}} 14. ^Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2008/2009 15. ^{{cite web|url=http://clinicaltrials.gov/ct2/show/NCT00673231|title=Efficacy and Safety of Dapagliflozin, Added to Therapy of Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov}} 16. ^{{cite web|url=http://ctr.bms.com/OneBmsCtd/InitTrialDetailAction.do?pnum=MB102-020|title=Bristol-Myers Squibb - Our Company|website=ctr.bms.com}} External links
5 : Bristol-Myers Squibb|Chloroarenes|Glucosides|Phenol ethers|SGLT2 inhibitors |
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