China Factory directly Doxycycline Monohydrate 50 Mg - Apixaban – CPF manufacturers and suppliers

Factory directly Doxycycline Monohydrate 50 Mg - Apixaban – CPF

Short Description:

Product Detail

Product Tags

Feedback (2)

Innovation, good quality and reliability are the core values of our enterprise. These principles today extra than ever form the basis of our success as an internationally active mid-size organization for Doxycycline Monohydrate For Bv, Doxycycline Hyclate For Syphilis, Ticagrelor 90 Mg Tablet, We, with great passion and faithfulness, are willing to provide you with perfect services and striding forward with you to create a bright future.

Factory directly Doxycycline Monohydrate 50 Mg - Apixaban – CPF Detail:

Background

Apixaban is a highly selective and reversible inhibitor of Factor Xa with Ki values of 0.08 nM and 0.17 nM in human and rabbit, respectively[1].

Factor X, also known by the eponym Stuart–Prower factor, is an enzyme of the coagulation cascade. Factor X is activated, by hydrolysis, into factor Xa by both factor IX. Factor Xa is the activated form of the coagulation factorthrombokinase.Inhibiting Factor Xa could offer an alternate method for anticoagulation. Direct Xa inhibitors are popular anticoagulants [2].

In vitro: Apixabanhas exhibited a high degree of potency, selectivity, and efficacy on Factor Xa with Ki of 0.08 nM and 0.17 nM for Human Factor Xa and Rabbit Factor Xa, respectively [1]. Apixaban prolonged the clotting times of normal human plasma with the concentrations (EC2x) of 3.6, 0.37, 7.4 and 0.4 μM, which are required respectively to double the prothrombin time (PT), modified prothrombin time (mPT), activated partial thromboplastin time (APTT) and HepTest. Besides, Apixaban showed the highest potency in human and rabbit plasma, but less potency in rat and dog plasma in both the PT and APTT assays [3].

In vivo: Apixaban exihibited the excellent pharmacokinetics with very low clearance (Cl: 0.02 L kg-1h-1), and low volume of distribution (Vdss: 0.2 L/kg) in the dog. Besides, Apixaban also showed a moderate half-life with T1/2 of 5.8 hours and good oral bioavailability (F: 58%) [1]. In the arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT) and electrically mediated carotid arterial thrombosis (ECAT) rabbit models, Apixaban produced antithrombotic effects with EC50 of 270 nM, 110 nM and 70 nM in a dose-dependent manner[3]. Apixaban significantly inhibited factor Xa activity with an IC50 of 0.22 μM in rabbit ex vivo[4]. In chimpanzee, Apixaban also showed small volume of distribution (Vdss: 0.17 L kg-1), low systemic clearance (Cl: 0.018 L kg-1h-1), and good oral bioavailability (F: 59%) [5].

References:
Pinto D J P, Orwat M J, Koch S, et al. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl) phenyl)-4, 5, 6, 7-tetrahydro-1 H-pyrazolo [3, 4-c] pyridine-3-carboxamide (Apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa[J]. Journal of medicinal chemistry, 2007, 50(22): 5339-5356.
Sidhu P S. Direct Factor Xa Inhibitors as Anticoagulants[J].
Wong P C, Crain E J, Xin B, et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostaticstudies[J]. Journal of Thrombosis and Haemostasis, 2008, 6(5): 820-829.
Zhang D, He K, Raghavan N, et al. Metabolism, pharmacokinetics and pharmacodynamics of the factor Xa inhibitor apixaban in rabbits[J]. Journal of thrombosis and thrombolysis, 2010, 29(1): 70-80.
He K, Luettgen J M, Zhang D, et al. Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor[J]. European journal of drug metabolism and pharmacokinetics, 2011, 36(3): 129-139.

Apixaban is a highly selective and reversible inhibitor of Factor Xa with Ki values of 0.08 nM and 0.17 nM in human and rabbit, respectively[1].

Chemical structure

Apixaban