Tìm theo
Fondaparinux sodium
Các tên gọi khác (2) :
  • Arixtra
  • Methyl O-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranosyl-(1-4)-O-beta-D-glucopyranuronosyl-(1-4)-O-2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranosyl-(1-4)-O-2-O-sulfo-alpha-L-idopyranuronosyl-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranoside, decasodium salt
antithrombins, anticoagulants
Thuốc Gốc
Small Molecule
CAS: 114870-03-0
ATC: B01AX05
ĐG : GlaxoSmithKline Inc. , http://www.gsk.com
CTHH: C31H45N3Na10O49S8
PTK: 1730.097
Fondaparinux (Arixtra) is a synthetic pentasaccharide anticoagulant. 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 glycosaminoglycan heparin and heparan sulfate (HS). This monomeric sequence in heparin and HS is thought to form the high affinity binding site for the natural 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. Fondaparinux potentiates the neutralizing action of ATIII on activated Factor X 300-fold. Fondaparinux may be used: to prevent venous thromboembolism in patients who have undergone orthopedic surgery of the lower limbs (e.g. hip fracture, hip replacement and knee surgery); to prevent VTE in patients undergoing abdominal surgery who are are at high risk of thromboembolic complications; in the treatment of deep vein thrombosis (DVT) and pumonary embolism (PE); in the management of unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI); and in the management of ST segment elevation myocardial infarction (STEMI).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C31H45N3Na10O49S8
Phân tử khối
1730.097
Monoisotopic mass
1728.786427203
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-8/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
InChI Key
InChIKey=XEKSTYNIJLDDAZ-JASSWCPGSA-F
IUPAC Name
decasodium N-[(2R,3R,4R,5S,6R)-2-{[(2S,3S,4R,5R,6R)-2-carboxy-6-{[(2R,3R,4R,5R,6R)-6-{[(2R,3S,4S,5R,6R)-2-carboxy-4-hydroxy-6-{[(2R,3S,4R,5R,6S)-4-hydroxy-6-methoxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl]oxy}-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-4,5-dihydroxyoxan-3-yl]oxy}-4,5-dihydroxy-6-[(sulfonatooxy)methyl]oxan-3-yl]sulfamate
Traditional IUPAC Name
decasodium N-[(2R,3R,4R,5S,6R)-2-{[(2S,3S,4R,5R,6R)-2-carboxy-6-{[(2R,3R,4R,5R,6R)-6-{[(2R,3S,4S,5R,6R)-2-carboxy-4-hydroxy-6-{[(2R,3S,4R,5R,6S)-4-hydroxy-6-methoxy-5-(sulfonatoamino)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-5-(sulfonatooxy)oxan-3-yl]oxy}-5-(sulfonatoamino)-4-(sulfonatooxy)-2-[(sulfonatooxy)methyl]oxan-3-yl]oxy}-4,5-dihydroxyoxan-3-yl]oxy}-4,5-dihydroxy-6-[(sulfonatooxy)methyl]oxan-3-yl]sulfamate
SMILES
[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].CO[[email protected]]1O[[email protected]](COS([O-])(=O)=O)[[email protected]@H](O[[email protected]@H]2O[[email protected]]([[email protected]@H](O[[email protected]]3O[[email protected]](COS([O-])(=O)=O)[[email protected]@H](O[[email protected]@H]4O[[email protected]@H]([[email protected]@H](O[[email protected]]5O[[email protected]](COS([O-])(=O)=O)[[email protected]@H](O)[[email protected]](O)[[email protected]]5NS([O-])(=O)=O)[[email protected]](O)[[email protected]]4O)C(O)=O)[[email protected]](OS([O-])(=O)=O)[[email protected]]3NS([O-])(=O)=O)[[email protected]](O)[[email protected]]2OS([O-])(=O)=O)C(O)=O)[[email protected]](O)[[email protected]]1NS([O-])(=O)=O
logP
0.4
pKa (strongest acidic)
-3
PSA
828.12 Å2
Refractivity
246.87 m3·mol-1
Polarizability
119.2 Å3
Rotatable Bond Count
27
H Bond Acceptor Count
44
H Bond Donor Count
11
Physiological Charge
-10
Number of Rings
5
Bioavailability
0
MDDR-Like Rule
true
Dược Lực Học : Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%) (PMID 11794148, 12049860). At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment.
Cơ Chế Tác Dụng : Fondaparinux (Arixtra) is a synthetic pentasaccharide anticoagulant. 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 glycosaminoglycan heparin and heparan sulfate (HS). This monomeric sequence in heparin and HS is thought to form the high affinity binding site for the natural 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. Fondaparinux potentiates the neutralizing action of ATIII on activated Factor X 300-fold. Fondaparinux may be used: to prevent venous thromboembolism in patients who have undergone orthopedic surgery of the lower limbs (e.g. hip fracture, hip replacement and knee surgery); to prevent VTE in patients undergoing abdominal surgery who are are at high risk of thromboembolic complications; in the treatment of deep vein thrombosis (DVT) and pumonary embolism (PE); in the management of unstable angina (UA) and non-ST segment elevation myocardial infarction (NSTEMI); and in the management of ST segment elevation myocardial infarction (STEMI). The antithrombotic activity of fondaparinux is the result of ATIII-mediated selective inhibition of Factor Xa. By selectively binding to ATIII, Fondaparinux potentiates (about 300 times) the neutralization of Factor Xa by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade and thus inhibits thrombin formation and thrombus development. It is thought that fondaparinux is unlikely to induce thrombocytopenia via a heparin-induced thrombocytopenia (HIT)-like mechanism given its chemical structure (PMID 19825921). As a result, fondaparinux has been used as an alternative anticoagulant in heparin-induced thrombocytopenia (HIT) patients (PMID 19737996, 19432027, 18217156). However, it is important to note that rare cases of HIT have been reported in patients treated with fondaparinux (PMID 20351685, 20351686).
Dược Động Học :
▧ Absorption :
100% bioavailability when administered subcutaneously
▧ Volume of Distribution :
* 7 - 11 L (healthy adults), distributed primarily in blood
▧ Protein binding :
94% in vitro protein binding specifically to ATIII
▧ Metabolism :
Not metabolized
▧ Route of Elimination :
In individuals with normal kidney function, fondaparinux is eliminated in urine mainly as unchanged drug.
▧ Half Life :
17-21 hours
Độc Tính : As with other anticoagulants, the main concern is increased bleed risk. The risk of hemorrhage may increase with decreased renal function, body mass less than 50 kg, and moderate to severe hepatic function.
Chỉ Định : Approved for: (1) prophylaxis of VTE for up to one month post surgery in patients undergoing orthopedic surgery of the lower limbs such as hip fracture, hip replacement and knee surgery; (2) prophylaxis of VTE patients undergoing abdominal surgery who are at high risk of thromboembolic complications (e.g. patients undergoing abdominal cancer surgery); (3) treatment of acute DVT and PE; (4) management of UA and NSTEMI for the prevention of death and subsequent myocardial infarction (MI); and (5) management of STEMI for the prevention of death and myocardial reinfarction in patients who are managed with thrombolytics or who are initially to receive no form of reperfusion therapy. Fondaparinux should not be used as the sole anticoagulant during percutaneous coronary intervention (PCI) due to an increased risk of guiding catheter thrombosis.
Tương Tác Thuốc :
  • Drotrecogin alfa Drotrecogin alfa may increase the adverse effects of fondaparinux, resulting in excessive bleeding. Concomitant use should be avoided.
  • Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Liều Lượng & Cách Dùng : Solution - Subcutaneous - 10 mg/0.8 ml
Solution - Subcutaneous - 2.5 mg/0.5 ml
Solution - Subcutaneous - 5 mg/0.4 ml
Solution - Subcutaneous - 7.5 mg/0.6 ml
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