| Revision as of 12:49, 17 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456579269 of page Fondaparinux for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL'). |
Latest revision as of 10:19, 16 August 2023 edit OAbot (talk | contribs)Bots440,440 editsm Open access bot: doi updated in citation with #oabot. |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 461103072 |
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| image = Fondaparinux.svg |
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| image = Fondaparinux.svg |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = Arixtra |
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| Drugs.com = {{drugs.com|monograph|arixtra}} |
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| Drugs.com = {{drugs.com|monograph|arixtra}} |
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| licence_EU = Arixtra |
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| licence_EU = yes |
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| licence_US = Fondaparinux |
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| DailyMedID = Fondaparinux |
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| pregnancy_category = |
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| pregnancy_category = |
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| routes_of_administration = ] |
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| ATC_prefix = B01 |
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| ATC_suffix = AX05 |
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| ATC_supplemental = |
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| legal_AU = S4 |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| legal_status = |
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| legal_EU = Rx-only |
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| legal_status = |
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| routes_of_administration = subcutaneous |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| protein_bound = 94% |
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| protein_bound = 94% |
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| metabolism = renally excreted unchanged |
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| metabolism = renally excreted unchanged |
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| elimination_half-life = 17-21 hours<ref name="Walenga Jeske Fareed 2005 pp. 143–177">{{cite book | vauthors = Walenga JM, Jeske WP, Fareed J | title=Chemistry and Biology of Heparin and Heparan Sulfate | chapter=Biochemical and Pharmacologic Rationale for Synthetic Heparin Polysaccharides | publisher=Elsevier | year=2005 | isbn=978-0-08-044859-6 | doi=10.1016/b978-008044859-6/50006-x | pages=143–177|quote=The elimination half-life of AT-bound fondaparinux is 17–21 h (171,172). The subcutaneous bioavailability of fondaparinux is nearly 100% and it is distributed mainly in the blood (165,173).}}</ref> |
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| elimination_half-life = 17-21 hours |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = 114870-03-0 |
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| CAS_number = 104993-28-4 |
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| ATC_prefix = B01 |
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| CAS_number2_Ref = {{cascite|correct|CAS}} |
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| ATC_suffix = AX05 |
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| CAS_number2 = 114870-03-0 |
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| ATC_supplemental = |
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| PubChem = 636380 |
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| PubChem = 636380 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00569 |
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| DrugBank = DB00569 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 552174 |
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| ChemSpiderID = 552174 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = J177FOW5JL |
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| UNII = J177FOW5JL |
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| UNII2_Ref = {{fdacite|correct|FDA}} |
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| ChEMBL = <!-- blanked - oldvalue: 1201202 --> |
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| UNII2 = X0Q6N9USOZ |
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| C=31 | H=43 | N=3 | Na=10 | O=49 | S=8 |
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| index2_label= decasodium salt |
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| molecular_weight = 1726.77 g/mol |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1201202 |
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<!--Chemical data--> |
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| C=31 | H=43 | N=3 | Na=10 | O=49 | S=8 |
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| SMILES = ..........S(=O)(=O)N5(O)(O)(COS()(=O)=O)O5O1(O)(O)(O1C()=O)O4(COS()(=O)=O)O(O3(O)(OS()(=O)=O)(O2(O)(NS()(=O)=O)(OC)O2COS()(=O)=O)O3C()=O)(NS()(=O)=O)4OS()(=O)=O |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C31H53N3O49S8.10Na/c1-69-27-9(33-85(48,49)50)13(37)17(6(74-27)3-71-88(57,58)59)76-31-22(83-91(66,67)68)16(40)21(24(81-31)26(43)44)79-29-10(34-86(51,52)53)19(82-90(63,64)65)18(7(75-29)4-72-89(60,61)62)77-30-15(39)14(38)20(23(80-30)25(41)42)78-28-8(32-84(45,46)47)12(36)11(35)5(73-28)2-70-87(54,55)56;;;;;;;;;;/h5-24,27-40H,2-4H2,1H3,(H,41,42)(H,43,44)(H,45,46,47)(H,48,49,50)(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62)(H,63,64,65)(H,66,67,68);;;;;;;;;;/q;10*+1/p-10/t5-,6-,7-,8-,9-,10-,11-,12-,13-,14-,15-,16+,17-,18-,19-,20+,21+,22-,23+,24-,27+,28-,29-,30-,31-;;;;;;;;;;/m1........../s1 |
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| StdInChI = 1S/C31H53N3O49S8.10Na/c1-69-27-9(33-85(48,49)50)13(37)17(6(74-27)3-71-88(57,58)59)76-31-22(83-91(66,67)68)16(40)21(24(81-31)26(43)44)79-29-10(34-86(51,52)53)19(82-90(63,64)65)18(7(75-29)4-72-89(60,61)62)77-30-15(39)14(38)20(23(80-30)25(41)42)78-28-8(32-84(45,46)47)12(36)11(35)5(73-28)2-70-87(54,55)56;;;;;;;;;;/h5-24,27-40H,2-4H2,1H3,(H,41,42)(H,43,44)(H,45,46,47)(H,48,49,50)(H,51,52,53)(H,54,55,56)(H,57,58,59)(H,60,61,62)(H,63,64,65)(H,66,67,68);;;;;;;;;;/q;10*+1/p-10/t5-,6-,7-,8-,9-,10-,11-,12-,13-,14-,15-,16+,17-,18-,19-,20+,21+,22-,23+,24-,27+,28-,29-,30-,31-;;;;;;;;;;/m1........../s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = XEKSTYNIJLDDAZ-JASSWCPGSA-D |
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| StdInChIKey = XEKSTYNIJLDDAZ-JASSWCPGSA-D |
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}} |
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}} |
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'''Fondaparinux''' (trade name '''Arixtra''') is an ] medication chemically related to ]s. It is marketed by ]. A generic version developed by Alchemia is marketed within the US by ]. |
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==Medical uses== |
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Clinically, it is used for the prevention of ] in patients who have had orthopedic surgery<ref>{{cite journal | vauthors = Fuji T, Fujita S, Ochi T | title = Fondaparinux prevents venous thromboembolism after joint replacement surgery in Japanese patients | journal = International Orthopaedics | volume = 32 | issue = 4 | pages = 443–451 | date = August 2008 | pmid = 17468868 | pmc = 2532275 | doi = 10.1007/s00264-007-0360-7 }}</ref> as well as for the treatment of deep vein thrombosis and ].<ref>{{Cite web |date=2018-09-17 |title=Arixtra |url=https://www.ema.europa.eu/en/medicines/human/EPAR/arixtra |access-date=2023-04-03 | work = European Medicines Agency |language=en}}</ref> |
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Fondaparinux is similar to ] in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long-term mortality and morbidity.<ref name="urlNEJM -- Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes">{{cite journal | vauthors = Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA | collaboration = Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators | display-authors = 6 | title = Comparison of fondaparinux and enoxaparin in acute coronary syndromes | journal = The New England Journal of Medicine | volume = 354 | issue = 14 | pages = 1464–1476 | date = April 2006 | pmid = 16537663 | doi = 10.1056/NEJMoa055443 | hdl-access = free | hdl = 2437/113091 }}</ref> |
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It has been investigated for use in conjunction with ].<ref name="Peters_2008">{{cite journal | vauthors = Peters RJ, Joyner C, Bassand JP, Afzal R, Chrolavicius S, Mehta SR, Oldgren J, Wallentin L, Budaj A, Fox KA, Yusuf S | display-authors = 6 | title = The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial | journal = European Heart Journal | volume = 29 | issue = 3 | pages = 324–331 | date = February 2008 | pmid = 18245119 | doi = 10.1093/eurheartj/ehm616 | doi-access = }}</ref> |
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===Comparison to other agents=== |
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One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for ] (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anti-coagulate patients with established HIT as it has no affinity for ]. However, its renal excretion precludes its use in patients with renal dysfunction. |
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Unlike ]s, it mediates its effects indirectly through ], but unlike ], it is selective for ]a.<ref name="pmid12820819">{{cite journal | vauthors = Comp PC | title = Selective factor Xa inhibition improves efficacy of venous thromboembolism prophylaxis in orthopedic surgery | journal = Pharmacotherapy | volume = 23 | issue = 6 | pages = 772–87 | date = June 2003 | pmid = 12820819 | doi = 10.1592/phco.23.6.772.32190 | s2cid = 19516097 | url = http://www.medscape.com/viewarticle/456874_5 }}</ref> |
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== Pharmacology == |
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=== Mechanism of action === |
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{{see also|Heparin#Mechanism of action}} |
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Fondaparinux is a synthetic pentasaccharide ] inhibitor. Fondaparinux binds ] and accelerates its inhibition of factor Xa. |
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Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric ]s ] and ] (HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high-affinity binding site for the anti-coagulant factor ] (AT). Binding of heparin or HS to AT has been shown to increase the anti-coagulant activity of antithrombin 1000 fold. In contrast to heparin, fondaparinux does not inhibit ]. |
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==Chemistry== |
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===Abbreviations=== |
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* '''GlcNS6S''' = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside |
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* '''GlcA''' = ] |
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* '''GlcNS3,6S''' = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl |
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* '''IdoA2S''' = ] |
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* '''GlcNS6SOMe''' = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside |
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Fondaparinux is only accessible by chemical synthesis. Recently, Supriya Dey ''et al''. reported an effective and scalable one-pot synthesis of Fondaparinux.<ref name="pmid32496799">{{cite journal | vauthors = Dey S, Lo HJ, Wong CH | title = Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux | journal = Organic Letters | volume = 22 | issue = 12 | pages = 4638–4642 | date = June 2020 | pmid = 32496799 | doi = 10.1021/acs.orglett.0c01386 | pmc = 7347301 | doi-access = free }}</ref> |
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The sequence of monosaccharides is D-GlcNS6S-α-(1,4)-D-GlcA-β-(1,4)-D-GlcNS3,6S-α-(1,4)-L-IdoA2S-α-(1,4)-D-GlcNS6S-OMe, as shown in the following structure: |
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] |
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== References == |
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{{reflist}} |
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== External links == |
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* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/fondaparinux | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Fondaparinux }} |
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{{Antithrombotics}} |
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{{GlaxoSmithKline}} |
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{{Portal bar | Medicine}} |
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] |
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] |