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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| Watchedfields = changed
| Watchedfields = changed
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<!--Identifiers-->
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 149920-56-9
| CAS_number = 162610-17-5
| ATC_prefix = none
| ATC_prefix = none
| ATC_suffix =
| ATC_suffix =
Line 35: Line 36:
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2340656
| ChemSpiderID = 2340656
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6ADD3H8MFZ


<!--Chemical data-->
<!--Chemical data-->
| chemical_formula =
| chemical_formula =
| C=38 | H=55 | Na=9 | O=49 | S=7
| C=38 | H=55 | Na=9 | O=49 | S=7
| molecular_weight = 1727.17683 g/mol
| smiles = CO[C@@H]1[C@H](O[C@@H]([C@@H]([C@H]1OC)OC)O[C@H]2[C@@H]([C@H]([C@@H](O[C@@H]2C(=O)[O-])O[C@@H]3[C@H](O[C@@H]([C@@H]([C@H]3OS(=O)(=O)[O-])OS(=O)(=O)[O-])O[C@H]4[C@@H]([C@H]([C@@H](O[C@H]4C(=O)[O-])O[C@@H]5[C@H](O[C@@H]([C@@H]([C@H]5OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC)COS(=O)(=O)[O-])OC)OC)COS(=O)(=O)[O-])OC)OC)COS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
| smiles = CO[C@@H]1[C@H](O[C@@H]([C@@H]([C@H]1OC)OC)O[C@H]2[C@@H]([C@H]([C@@H](O[C@@H]2C(=O)[O-])O[C@@H]3[C@H](O[C@@H]([C@@H]([C@H]3OS(=O)(=O)[O-])OS(=O)(=O)[O-])O[C@H]4[C@@H]([C@H]([C@@H](O[C@H]4C(=O)[O-])O[C@@H]5[C@H](O[C@@H]([C@@H]([C@H]5OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC)COS(=O)(=O)[O-])OC)OC)COS(=O)(=O)[O-])OC)OC)COS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
| InChI = 1/C38H64O49S7.9Na/c1-64-15-12(9-72-88(43,44)45)76-35(27(68-5)18(15)65-2)80-21-19(66-3)28(69-6)37(82-25(21)32(39)40)79-17-14(11-74-90(49,50)51)77-38(31(87-94(61,62)63)24(17)85-92(55,56)57)81-22-20(67-4)29(70-7)36(83-26(22)33(41)42)78-16-13(10-73-89(46,47)48)75-34(71-8)30(86-93(58,59)60)23(16)84-91(52,53)54;;;;;;;;;/h12-31,34-38H,9-11H2,1-8H3,(H,39,40)(H,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63);;;;;;;;;/q;9*+1/p-9/t12-,13-,14-,15-,16-,17-,18+,19+,20+,21+,22+,23+,24+,25+,26-,27-,28-,29-,30-,31-,34+,35-,36-,37-,38-;;;;;;;;;/m1........./s1
| InChIKey = MVPQUSQUURLQKF-KRAUNZEEBS
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C38H64O49S7.9Na/c1-64-15-12(9-72-88(43,44)45)76-35(27(68-5)18(15)65-2)80-21-19(66-3)28(69-6)37(82-25(21)32(39)40)79-17-14(11-74-90(49,50)51)77-38(31(87-94(61,62)63)24(17)85-92(55,56)57)81-22-20(67-4)29(70-7)36(83-26(22)33(41)42)78-16-13(10-73-89(46,47)48)75-34(71-8)30(86-93(58,59)60)23(16)84-91(52,53)54;;;;;;;;;/h12-31,34-38H,9-11H2,1-8H3,(H,39,40)(H,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63);;;;;;;;;/q;9*+1/p-9/t12-,13-,14-,15-,16-,17-,18+,19+,20+,21+,22+,23+,24+,25+,26-,27-,28-,29-,30-,31-,34+,35-,36-,37-,38-;;;;;;;;;/m1........./s1
| StdInChI = 1S/C38H64O49S7.9Na/c1-64-15-12(9-72-88(43,44)45)76-35(27(68-5)18(15)65-2)80-21-19(66-3)28(69-6)37(82-25(21)32(39)40)79-17-14(11-74-90(49,50)51)77-38(31(87-94(61,62)63)24(17)85-92(55,56)57)81-22-20(67-4)29(70-7)36(83-26(22)33(41)42)78-16-13(10-73-89(46,47)48)75-34(71-8)30(86-93(58,59)60)23(16)84-91(52,53)54;;;;;;;;;/h12-31,34-38H,9-11H2,1-8H3,(H,39,40)(H,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63);;;;;;;;;/q;9*+1/p-9/t12-,13-,14-,15-,16-,17-,18+,19+,20+,21+,22+,23+,24+,25+,26-,27-,28-,29-,30-,31-,34+,35-,36-,37-,38-;;;;;;;;;/m1........./s1
Line 50: Line 50:
<!-- MeSHName=SANORG+34006 -->
<!-- MeSHName=SANORG+34006 -->


'''Idraparinux sodium''' is an [[anticoagulant]] medication in development by [[Sanofi-Aventis]].<ref name="pmid18294998">{{cite journal |author=Bousser MG, Bouthier J, Büller HR, ''et al.'' |title=Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial |journal=Lancet |volume=371 |issue=9609 |pages=315–21 |date=January 2008 |pmid=18294998 |doi=10.1016/S0140-6736(08)60168-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)60168-3}}</ref>
'''Idraparinux sodium''' is an [[anticoagulant]] medication in development by [[Sanofi-Aventis]].<ref name="pmid18294998">{{cite journal |vauthors=Bousser MG, Bouthier J, Büller HR, etal |title=Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial |journal=Lancet |volume=371 |issue=9609 |pages=315–21 |date=January 2008 |pmid=18294998 |doi=10.1016/S0140-6736(08)60168-3 |s2cid=37919 }}</ref>


It has a similar chemical structure and the same method of action as [[fondaparinux]], but with an elimination half-life about five to six times longer (an increase from fondaparinux's 17 hours to approximately 80 hours), which means that the drug should only need to be injected once a week.
It has a similar chemical structure and the same method of action as [[fondaparinux]], but with an elimination half-life about five to six times longer (an increase from fondaparinux's 17 hours to approximately 80 hours), which means that the drug should only need to be injected once a week. Supriya Dey et al recently reported shortest chemical synthesis of Idraparinux for the large-scale production.{{Cn|date=January 2024}}


Sanofi discontinued the development of idraparinux sodium.
{{as of|July 2007}}, it has completed the [[Phase III clinical trial]] AMADEUS.


==Negative clinical trial==
==Negative clinical trial==
A phase III trial of idraparinux sodium for stroke prevention in patients with AF was halted prematurely due to excessive clinically relevant bleeding. Sanofi discontinued the development of idraparinux sodium in favour of a biotinylated formulation of the drug called idrabiotaparinux sodium.<ref>Modern anticoagulants threaten status quo http://www.pmlive.com/pharma_intelligence/modern_anticoagulants_threaten_status_quo_411610</ref>
A phase III trial of idraparinux sodium for stroke prevention in patients with AF (AMADEUS) was halted prematurely due to excessive clinically relevant and intracranial bleeding. Bleedings were particularly increased in elderly patients and those with renal impairment. Sanofi discontinued the development of idraparinux sodium in favour of a biotinylated formulation of the drug called idrabiotaparinux sodium.<ref>Modern anticoagulants threaten status quo http://www.pmlive.com/pharma_intelligence/modern_anticoagulants_threaten_status_quo_411610</ref><ref>The Amadeus investigators. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008; 371:315-321. </ref>


==Method of action==
==Method of action==
Idraparinux selectively blocks [[coagulation factor Xa]].<ref name="pmid17855670">{{cite journal |author=Buller HR, Cohen AT, Davidson B, ''et al.'' |title=Idraparinux versus standard therapy for venous thromboembolic disease |journal=N. Engl. J. Med. |volume=357 |issue=11 |pages=1094–104 |date=September 2007 |pmid=17855670 |doi=10.1056/NEJMoa064247 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=17855670&promo=ONFLNS19}}</ref>
Idraparinux selectively blocks [[coagulation factor Xa]].<ref name="pmid17855670">{{cite journal |vauthors=Buller HR, Cohen AT, Davidson B, etal |title=Idraparinux versus standard therapy for venous thromboembolic disease |journal=N. Engl. J. Med. |volume=357 |issue=11 |pages=1094–104 |date=September 2007 |pmid=17855670 |doi=10.1056/NEJMoa064247 |doi-access=free }}</ref>


See [[Heparin#Mechanism of anticoagulant action|Heparin: Mechanism of anticoagulant action]] for a comparison of the mechanism of heparin, low-molecular-weight heparins, fondaparinux and idraparinux.
See [[Heparin#Mechanism of anticoagulant action|Heparin: Mechanism of anticoagulant action]] for a comparison of the mechanism of heparin, low-molecular-weight heparins, fondaparinux and idraparinux.


== {{anchor|Idrabiotaparinux}} Idrabiotaparinux ==
==Spin off idrabiotaparinux sodium==
Idrabiotaparinux sodium is also administered once-weekly. It has the same pentasaccharidic structure as idraparinux sodium, but with [[biotin]] attached, which allows its neutralisation with [[avidin]], an egg-derived protein with low antigenicity.
Sanofi conducted three phase III trials of idrabiotaparinux sodium between 2006 and 2008 in approximately 13,550 patients. In one phase III trial, idrabiotaparinux sodium was non-inferior to warfarin in preventing the recurrent VTE at three months in patients with pulmonary embolism and the incidence of clinically relevant bleeding was lower in the idrabiotaparinux sodium arm. The drug was expected to be filed for stroke prevention in patients with AF in 2011. However, Sanofi has since discontinued its development. The company announced in May 2011 that the drug is available for licensing. <ref>Modern anticoagulants threaten status quo http://www.pmlive.com/pharma_intelligence/modern_anticoagulants_threaten_status_quo_411610</ref>
Sanofi conducted three phase III trials of idrabiotaparinux sodium between 2006 and 2008 in approximately 13,550 patients. In one phase III trial (the BOREALIS-AF study), idrabiotaparinux sodium was non-inferior to warfarin in preventing the recurrent [[venous thromboembolism]] at three months in patients with pulmonary embolism and the incidence of clinically relevant bleeding was lower in the idrabiotaparinux sodium arm. The drug was expected to be filed for stroke prevention in patients with [[atrial fibrillation]] in 2011. The study was prematurely terminated, and the reason remains unclear.<ref>Stroke Prevention in Atrial Fibrillation: Latest Clinical Trials and Guidelines Luciana Armaganijan, Dimpi Patel, [...], and Carlos A. Morillo Pharmaceuticals (Basel). Apr 2012; 5(4): 384–397 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3763643/#!po=2.63158 doi: 10.3390/ph5040384]</ref> However, Sanofi has since discontinued its development. The company announced in May 2011 that the drug is available for licensing.<ref>Modern anticoagulants threaten status quo http://www.pmlive.com/pharma_intelligence/modern_anticoagulants_threaten_status_quo_411610</ref> A systematic review found that until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux are as effective and safe as the standard warfarin treatment for venous thromboembolism prevention. Idraparinux or idrabiotaparinux decreased major bleeding rate significantly but had a trend to increase the all-cause mortality compared with warfarin.<ref>Song Y, Li X, Pavithra S, Li D (2013) Idraparinux or Idrabiotaparinux for Long-Term Venous Thromboembolism Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS ONE 8(11): e78972. [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078972 doi:10.1371/journal.pone.0078972]</ref>


==References==
==References==
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[[Category:Oligosaccharides]]
[[Category:Oligosaccharides]]
[[Category:Heparins]]
[[Category:Heparins]]
8. Supriya Dey, Hong Jay Lo and Chi Huey Wong “ An efficient Modular One pot synthesis of Heparin-Based Anticoagulant Idraparinux” J. Am. Chem. Soc. 2019, 141, 10309

Latest revision as of 19:13, 6 January 2024

Idraparinux
Clinical data
Routes of
administration		Subcutaneous
ATC code
  • none
Legal status
Legal status
  • Investigational
Pharmacokinetic data
Elimination half-life80-130 hours
Identifiers
  • Nonasodium (2S,3S,4S,5R,6R)-6-[(2R,3R,4S,5R,6R)-6-
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC38H55Na9O49S7
Molar mass1727.14 g·mol−1
3D model (JSmol)
  • CO[C@@H]1[C@H](O[C@@H]([C@@H]([C@H]1OC)OC)O[C@H]2[C@@H]([C@H]([C@@H](O[C@@H]2C(=O)[O-])O[C@@H]3[C@H](O[C@@H]([C@@H]([C@H]3OS(=O)(=O)[O-])OS(=O)(=O)[O-])O[C@H]4[C@@H]([C@H]([C@@H](O[C@H]4C(=O)[O-])O[C@@H]5[C@H](O[C@@H]([C@@H]([C@H]5OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC)COS(=O)(=O)[O-])OC)OC)COS(=O)(=O)[O-])OC)OC)COS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
  • InChI=1S/C38H64O49S7.9Na/c1-64-15-12(9-72-88(43,44)45)76-35(27(68-5)18(15)65-2)80-21-19(66-3)28(69-6)37(82-25(21)32(39)40)79-17-14(11-74-90(49,50)51)77-38(31(87-94(61,62)63)24(17)85-92(55,56)57)81-22-20(67-4)29(70-7)36(83-26(22)33(41)42)78-16-13(10-73-89(46,47)48)75-34(71-8)30(86-93(58,59)60)23(16)84-91(52,53)54;;;;;;;;;/h12-31,34-38H,9-11H2,1-8H3,(H,39,40)(H,41,42)(H,43,44,45)(H,46,47,48)(H,49,50,51)(H,52,53,54)(H,55,56,57)(H,58,59,60)(H,61,62,63);;;;;;;;;/q;9*+1/p-9/t12-,13-,14-,15-,16-,17-,18+,19+,20+,21+,22+,23+,24+,25+,26-,27-,28-,29-,30-,31-,34+,35-,36-,37-,38-;;;;;;;;;/m1........./s1 checkY
  • Key:MVPQUSQUURLQKF-MCPDASDXSA-E checkY
  (verify)

Idraparinux sodium is an anticoagulant medication in development by Sanofi-Aventis.[1]

It has a similar chemical structure and the same method of action as fondaparinux, but with an elimination half-life about five to six times longer (an increase from fondaparinux's 17 hours to approximately 80 hours), which means that the drug should only need to be injected once a week. Supriya Dey et al recently reported shortest chemical synthesis of Idraparinux for the large-scale production.[citation needed]

Sanofi discontinued the development of idraparinux sodium.

Negative clinical trial

[edit]

A phase III trial of idraparinux sodium for stroke prevention in patients with AF (AMADEUS) was halted prematurely due to excessive clinically relevant and intracranial bleeding. Bleedings were particularly increased in elderly patients and those with renal impairment. Sanofi discontinued the development of idraparinux sodium in favour of a biotinylated formulation of the drug called idrabiotaparinux sodium.[2][3]

Method of action

[edit]

Idraparinux selectively blocks coagulation factor Xa.[4]

See Heparin: Mechanism of anticoagulant action for a comparison of the mechanism of heparin, low-molecular-weight heparins, fondaparinux and idraparinux.

Idrabiotaparinux

[edit]

Idrabiotaparinux sodium is also administered once-weekly. It has the same pentasaccharidic structure as idraparinux sodium, but with biotin attached, which allows its neutralisation with avidin, an egg-derived protein with low antigenicity. Sanofi conducted three phase III trials of idrabiotaparinux sodium between 2006 and 2008 in approximately 13,550 patients. In one phase III trial (the BOREALIS-AF study), idrabiotaparinux sodium was non-inferior to warfarin in preventing the recurrent venous thromboembolism at three months in patients with pulmonary embolism and the incidence of clinically relevant bleeding was lower in the idrabiotaparinux sodium arm. The drug was expected to be filed for stroke prevention in patients with atrial fibrillation in 2011. The study was prematurely terminated, and the reason remains unclear.[5] However, Sanofi has since discontinued its development. The company announced in May 2011 that the drug is available for licensing.[6] A systematic review found that until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux are as effective and safe as the standard warfarin treatment for venous thromboembolism prevention. Idraparinux or idrabiotaparinux decreased major bleeding rate significantly but had a trend to increase the all-cause mortality compared with warfarin.[7]

References

[edit]
  1. ^ Bousser MG, Bouthier J, Büller HR, et al. (January 2008). "Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial". Lancet. 371 (9609): 315–21. doi:10.1016/S0140-6736(08)60168-3. PMID 18294998. S2CID 37919.
  2. ^ Modern anticoagulants threaten status quo http://www.pmlive.com/pharma_intelligence/modern_anticoagulants_threaten_status_quo_411610
  3. ^ The Amadeus investigators. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial. Lancet 2008; 371:315-321.
  4. ^ Buller HR, Cohen AT, Davidson B, et al. (September 2007). "Idraparinux versus standard therapy for venous thromboembolic disease". N. Engl. J. Med. 357 (11): 1094–104. doi:10.1056/NEJMoa064247. PMID 17855670.
  5. ^ Stroke Prevention in Atrial Fibrillation: Latest Clinical Trials and Guidelines Luciana Armaganijan, Dimpi Patel, [...], and Carlos A. Morillo Pharmaceuticals (Basel). Apr 2012; 5(4): 384–397 doi: 10.3390/ph5040384
  6. ^ Modern anticoagulants threaten status quo http://www.pmlive.com/pharma_intelligence/modern_anticoagulants_threaten_status_quo_411610
  7. ^ Song Y, Li X, Pavithra S, Li D (2013) Idraparinux or Idrabiotaparinux for Long-Term Venous Thromboembolism Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS ONE 8(11): e78972. doi:10.1371/journal.pone.0078972

8. Supriya Dey, Hong Jay Lo and Chi Huey Wong “ An efficient Modular One pot synthesis of Heparin-Based Anticoagulant Idraparinux” J. Am. Chem. Soc. 2019, 141, 10309

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