Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/19 15:31:06」(JST)

wiki en

Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.

Structure and mechanism

Fondaparinux is a synthetic pentasaccharide Factor Xa inhibitor. 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 glycosaminoglycans heparin and heparin sulfate (HS). Within heparin and heparin sulfate this monomeric sequence is thought to form the high affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.

Administration

Fondaparinux is given subcutaneously daily. Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.

Comparison to other agents

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anticoagulate patients with established HIT as it has no affinity to PF-4. However, its renal excretion precludes its use in patients with renal dysfunction.

Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is selective for factor Xa.^[1]

Uses

Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.^[2]

It has been investigated for use in conjunction with streptokinase.^[3]

Chemical structure

Abbreviations

GlcNS6S = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside
GlcA = β-D-glucopyranuronoside
GlcNS3,6S = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl
IdoA2S = 2-O-sulfo-α-L-idopyranuronoside
GlcNS6SOMe = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside

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:

References

^ "Medscape.com". Retrieved 2009-01-23.
^ "NEJM -- Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes". Retrieved 2009-01-23.
^ Peters RJ, Joyner C, Bassand JP, et al. (February 2008). "The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial". Eur. Heart J. 29 (3): 324–31. doi:10.1093/eurheartj/ehm616. PMID 18245119.

The scientist couple Dr Joachim Seifert and Dr Latika 's hard work and dedicated research have led to the making of fondaparinux.They should be applauded for this remakable acheivement.

External links

Arixtra home page
Alchemia home page

UpToDate Contents

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. フォンダパリヌクスの治療使用 therapeutic use of fondaparinux
2. 静脈血栓塞栓症の患者における理論的根拠と無期限の抗凝固の適応 rationale and indications for indefinite anticoagulation in patients with venous thromboembolism
3. 急性肺塞栓症の抗凝固療法 anticoagulation in acute pulmonary embolism
4. 非ST上昇型急性冠症候群における抗凝固療法 anticoagulant therapy in non st elevation acute coronary syndromes
5. ヘパリン起因性血小板減少症のマネージメント management of heparin induced thrombocytopenia

English Journal

Prophylactic dose fondaparinux for 6 weeks in superficial thrombophlebitis of the legs reduces the risk for symptomatic thromboembolic complications.

Desancho MT, Pastores SM.SourceDepartment of Medicine, Weill Cornell Medical Center, New York, New York, USA.
Evidence-based medicine.Evid Based Med.2013 Feb;18(1):28-29. Epub 2012 Jun 27.
PMID 22740355

Effects of argatroban, danaparoid, and fondaparinux on trombin generation in heparin - induced thrombocytopenia.

Tardy-Poncet B, Combe M, Piot M, Chapelle C, Akrour M, Tardy B.SourceBrigitte Tardy-Poncet, Laboratoire d'Hématologie, CHU Saint Etienne, 42055 Saint Etienne cedex 2, France, Tel.: +33 4 77 82 85 91, Fax: +33 4 77 82 84 55, E-mail: brigitte.tardy@chu-st-etienne.fr.
Thrombosis and haemostasis.Thromb Haemost.2013 Jan 17;109(3). [Epub ahead of print]
There is no in vitro data on the comparison of the effects of danaparoid, argatroban and fondaparinux on thrombin generation in patients with heparin-induced thrombocytopenia. It was the study objective to compare the in vitro anticoagulant potential of argatroban, danaparoid and fondaparinux us
PMID 23328916

Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model.

An J, Waitara M, Bordas M, Arumugam V, Hoffmann RG, Petrich BG, Sinha U, North P, Sood R.SourceDivision of Pediatric Pathology, Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, United States;
Blood.Blood.2013 Jan 16. [Epub ahead of print]
Low Molecular Weight Heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven and
PMID 23325830

Japanese Journal

Spinal Epidural Hematoma during Anticoagulant Therapy for Pulmonary Embolism: Postoperative Complications in a Patient with Lung Cancer

Kobayashi Yoshihisa,Nakada Junya,Kuroda Hiroaki,Sakakura Noriaki,Usami Noriyasu,Sakao Yukinori
Annals of Thoracic and Cardiovascular Surgery 20(Supplement), 493-496, 2014
… Anticoagulant therapy with fondaparinux and warfarin was started 2 hours after epidural catheter removal and he gradually recovered. … On postoperative day 13, the level of prothrombin time-international normalized ratio reached 1.47 and fondaparinux administration was stopped. …
NAID 130004889740

Pharmacological effects and clinical applications of ultra low molecular weight heparins

Liu Zhang,Ji Shengli,Sheng Juzheng,Wang Fengshan
Drug Discoveries & Therapeutics 8(1), 1-10, 2014
… Fondaparinux, a chemically synthesized ULMWH of pentasaccharide, has the same antithrombin III (AT-III)-binding sequence as found in UFH and LMWH. … In this paper, we review the preparation process, pharmacological effects and clinical applications of fondaparinux, AVE5026 and RO-14. …
NAID 130003397393

Spinal Epidural Hematoma during Anticoagulant Therapy for Pulmonary Embolism: Postoperative Complications in a Patient with Lung Cancer

Kobayashi Yoshihisa,Nakada Junya,Kuroda Hiroaki,Sakakura Noriaki,Usami Noriyasu,Sakao Yukinori
Annals of Thoracic and Cardiovascular Surgery, 2014
… Anticoagulant therapy with fondaparinux and warfarin was started 2 hours after epidural catheter removal and he gradually recovered. … On postoperative day 13, the level of prothrombin time-international normalized ratio reached 1.47 and fondaparinux administration was stopped. …
NAID 130003396749

Related Pictures

★リンクテーブル★

リンク元	「フォンダパリヌクス」「フォンダパリナックス」
拡張検索	「fondaparinux sodium」

「フォンダパリヌクス」

Fondaparinux
Clinical data
Trade names	Arixtra
AHFS/Drugs.com	monograph
Licence data	EMA:Link, US FDA:link
Legal status	POM (UK) ℞-only (US)
Routes	subcutaneous
Pharmacokinetic data
Bioavailability	N/A
Protein binding	94%
Metabolism	renally excreted unchanged
Half-life	17-21 hours
Identifiers
CAS number	114870-03-0
ATC code	B01AX05
PubChem	CID 636380
DrugBank	DB00569
ChemSpider	552174
UNII	J177FOW5JL
ChEMBL	CHEMBL1201202
Chemical data
Formula	C31H43N3Na10O49S8
Mol. mass	1726.77 g/mol
	InChI InChI=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 ; Key:XEKSTYNIJLDDAZ-JASSWCPGSA-D ;
(what is this?) (verify)

　　[★]

英: fondaparinux
同: フォンダパリナックス
化: fondaparinux sodium フォンダパリヌクスナトリウム、フォンダパリナックスナトリウム
商: アリクストラ
関: 血液凝固阻止剤

抗血栓薬

特徴

構造

作用機序

ATIIIに高親和性に結合してATIIIの抗第Xa因子活性を増強させる
第Xa因子活性：↓
抗トロンビン活性：↓

薬理作用

抗菌スペクトル

動態

適応

注意

禁忌

副作用

「フォンダパリナックス」

　　[★]

英: fondaparinux
関: フォンダパリヌクス

「fondaparinux sodium」

　　[★] フォンダパリヌクス

[1] "Medscape.com". Retrieved 2009-01-23.

[urlNEJM_--_Comparison_of_Fondaparinux_and_Enoxaparin_in_Acute_Coronary_Syndromes-2] "NEJM -- Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes". Retrieved 2009-01-23.

[pmid18245119-3] Peters RJ, Joyner C, Bassand JP, et al. (February 2008). "The role of fondaparinux as an adjunct to thrombolytic therapy in acute myocardial infarction: a subgroup analysis of the OASIS-6 trial". Eur. Heart J. 29 (3): 324–31. doi:10.1093/eurheartj/ehm616. PMID 18245119.

匿名

検索

案内

案内

fondaparinux