Background

Apixaban inosarudzika uye inodzoreredzwa inhibitor yeFactor Xa ine Ki values ​​dze0.08 nM uye 0.17 nM mumunhu netsuro, zvichiteerana[1].

Factor X, inozivikanwawo neiyo eponym Stuart-Prower factor, ienzyme yeiyo coagulation cascade. Factor X inogadziriswa, ne hydrolysis, kuita chinhu Xa nezvose zviri zviviri factor IX. Factor Xa is the activated form of the coagulation factorthrombokinase.Inhibiting Factor Xa inogona kupa imwe nzira yeanticoagulation. Direct Xa inhibitors anozivikanwa anticoagulants [2].

In vitro: Apixabanhas yakaratidza huwandu hwepamusoro hwesimba, kusarudza, uye kushanda paFactor Xa ine Ki ye 0.08 nM uye 0.17 nM yeHuman Factor Xa uye Rabbit Factor Xa, maererano [1]. Apixaban yakawedzera nguva yekuvhara kweplasma yemunhu yakajairwa nehuwandu (EC2x) ye3.6, 0.37, 7.4 uye 0.4 μM, iyo inodiwa zvakatevedzana kupeta nguva yeprothrombin (PT), yakagadziridzwa prothrombin nguva (mPT), activated partial thromboplastin time ( APTT) uye HepTest. Kunze kwezvo, Apixaban yakaratidza simba repamusoro-soro muplasma yevanhu uye tsuro, asi simba shoma mumakonzo uye imbwa plasma mune zvose PT uye APTT assays [3].

In vivo: Apixaban yakaratidza yakanakisa pharmacokinetics ine yakaderera kwazvo clearance (Cl: 0.02 L kg-1h-1), uye yakaderera vhoriyamu yekugovera (Vdss: 0.2 L / kg) mumbwa. Kunze kwezvo, Apixaban yakaratidzawo mwero hafu yehupenyu neT1 / 2 yemaawa 5.8 uye yakanaka yemuromo bioavailability (F: 58%) [1]. Mu arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT) uye magetsi anoshandiswa carotid arterial thrombosis (ECAT) tsuro mhando, Apixaban yakagadzira antithrombotic mhedzisiro ine EC50 ye270 nM, 110 nM uye 70 nM nenzira inotsamira mudosi [3. ]. Apixaban yakanyanya inhibited factor Xa chiitiko neIC50 ye0.22 μM mune tsuro ex vivo[4]. Muchimpanzee, Apixaban yakaratidzawo zvishoma kugoverwa (Vdss: 0.17 L kg-1), pasi systemic clearance (Cl: 0.018 L kg-1h-1), uye yakanaka yemuromo bioavailability (F: 59%) [5].

References:
Pinto DJP, Orwat MJ, Koch S, et al. Kuwanikwa kwe1-(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), ine simba kwazvo, inosarudza, inoshanda, uye orally bioavailable inhibitor yeropa coagulation factor Xa[J]. Nyaya yemishonga yemakemikari, 2007, 50 (22): 5339-5356.
Sidhu P S. Direct Factor Xa Inhibitors seAnticoagulants[J].
Wong PC, Crain EJ, Xin B, et al. Apixaban, yemuromo, yakananga uye yakanyanya kusarudza chinhu Xa inhibitor: in vitro, antithrombotic uye antihemostaticstudies[J]. Nyaya yeThrombosis uye Haemostasis, 2008, 6 (5): 820-829.
Zhang D, He K, Raghavan N, et al. Metabolism, pharmacokinetics uye pharmacodynamics yefactor Xa inhibitor apixaban mutsuro[J]. Nyaya ye thrombosis uye thrombolysis, 2010, 29 (1): 70-80.
Iye K, Luettgen JM, Zhang D, et al. Preclinical pharmacokinetics uye pharmacodynamics yeapixaban, ine simba uye yakasarudzwa chinhu Xa inhibitor[J]. European Journal yezvinodhaka metabolism uye pharmacokinetics, 2011, 36 (3): 129-139.

Apixaban inosarudzika uye inodzoreredzwa inhibitor yeFactor Xa ine Ki values ​​dze0.08 nM uye 0.17 nM mumunhu netsuro, zvichiteerana[1].

Factor X, inozivikanwawo neiyo eponym Stuart-Prower factor, ienzyme yeiyo coagulation cascade. Factor X inogadziriswa, ne hydrolysis, kuita chinhu Xa nezvose zviri zviviri factor IX. Factor Xa is the activated form of the coagulation factorthrombokinase.Inhibiting Factor Xa inogona kupa imwe nzira yeanticoagulation. Direct Xa inhibitors anozivikanwa anticoagulants [2].

In vitro: Apixabanhas yakaratidza huwandu hwepamusoro hwesimba, kusarudza, uye kushanda paFactor Xa ine Ki ye 0.08 nM uye 0.17 nM yeHuman Factor Xa uye Rabbit Factor Xa, maererano [1]. Apixaban yakawedzera nguva yekuvhara kweplasma yemunhu yakajairwa nehuwandu (EC2x) ye3.6, 0.37, 7.4 uye 0.4 μM, iyo inodiwa zvakatevedzana kupeta nguva yeprothrombin (PT), yakagadziridzwa prothrombin nguva (mPT), activated partial thromboplastin time ( APTT) uye HepTest. Kunze kwezvo, Apixaban yakaratidza simba repamusoro-soro muplasma yevanhu uye tsuro, asi simba shoma mumakonzo uye imbwa plasma mune zvose PT uye APTT assays [3].

In vivo: Apixaban yakaratidza yakanakisa pharmacokinetics ine yakaderera kwazvo clearance (Cl: 0.02 L kg-1h-1), uye yakaderera vhoriyamu yekugovera (Vdss: 0.2 L / kg) mumbwa. Kunze kwezvo, Apixaban yakaratidzawo mwero hafu yehupenyu neT1 / 2 yemaawa 5.8 uye yakanaka yemuromo bioavailability (F: 58%) [1]. Mu arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT) uye magetsi anoshandiswa carotid arterial thrombosis (ECAT) tsuro mhando, Apixaban yakagadzira antithrombotic mhedzisiro ine EC50 ye270 nM, 110 nM uye 70 nM nenzira inotsamira mudosi [3. ]. Apixaban yakanyanya inhibited factor Xa chiitiko neIC50 ye0.22 μM mune tsuro ex vivo[4]. Muchimpanzee, Apixaban yakaratidzawo zvishoma kugoverwa (Vdss: 0.17 L kg-1), pasi systemic clearance (Cl: 0.018 L kg-1h-1), uye yakanaka yemuromo bioavailability (F: 59%) [5].

References:
Pinto DJP, Orwat MJ, Koch S, et al. Kuwanikwa kwe1-(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), ine simba kwazvo, inosarudza, inoshanda, uye orally bioavailable inhibitor yeropa coagulation factor Xa[J]. Nyaya yemishonga yemakemikari, 2007, 50 (22): 5339-5356.
Sidhu P S. Direct Factor Xa Inhibitors seAnticoagulants[J].
Wong PC, Crain EJ, Xin B, et al. Apixaban, yemuromo, yakananga uye yakanyanya kusarudza chinhu Xa inhibitor: in vitro, antithrombotic uye antihemostaticstudies[J]. Nyaya yeThrombosis uye Haemostasis, 2008, 6 (5): 820-829.
Zhang D, He K, Raghavan N, et al. Metabolism, pharmacokinetics uye pharmacodynamics yefactor Xa inhibitor apixaban mutsuro[J]. Nyaya ye thrombosis uye thrombolysis, 2010, 29 (1): 70-80.
Iye K, Luettgen JM, Zhang D, et al. Preclinical pharmacokinetics uye pharmacodynamics yeapixaban, ine simba uye yakasarudzwa chinhu Xa inhibitor[J]. European Journal yezvinodhaka metabolism uye pharmacokinetics, 2011, 36 (3): 129-139.

Chimiro chemakemikari