在膜片钳 hERG 测试中，betrixaban (PRT054021) 的 IC50 为 8.9 μM[1]。 Betrixaban 对血浆激肽释放酶的 IC50 和 Ki 分别为 6.3 μM 和 3.5 μM[1]。与所有其他药物 (hERG Ki⩽0.5 μM) 相比，betrixaban (hERG Ki 1.8 μM) 显示出明显较低的 hERG 活性[1]。 Betrixaban 抑制凝血酶的产生 (5–25 ng/mL)[3]。

在犬中，贝曲西班的口服生物利用度为 51.6%（0.5 mg/kg，静脉注射；2.5 mg/kg，口服）[1]。在猴子中，贝曲西班的口服生物利用度为 58.7%（0.75 mg/kg，静脉注射；7.5 mg/kg，口服）[1]。 R-Antidote 可逆转贝曲西班介导的全血 INR 升高。 30 分钟静脉输注后，贝曲西班的总血浆浓度为 0.2±0.01 μM，其中 40%±7.2% 的抑制剂保持未结合。 r-Antidote 递送后，未结合抑制剂的比例下降至 0.3%±0.1%，而总血浆浓度上升至 2.0±0.4 μM[2]。当用于棉线上血栓积聚的兔腹部腔静脉模型时，贝曲西班 (3 mg/kg) 对血栓质量的抑制作用与依诺肝素 1.6 mg/kg 几乎相同（76% 与 96% 抑制作用）[3]。在大鼠颈动脉的氯化铁损伤模型中，贝曲西班 (19.1 mg/kg) 至少与依诺肝素 7.6 mg/kg 和氯吡格雷 3 mg/kg/d 一样有效（90% vs. 70% vs. 80% 通畅率）分别）保持通畅[3]。

Absorption, Distribution and Excretion
Betrixaban presents a rapid absorption at a dose of 80 mg. Its peak plasma concentration is registered within 3-4 hours after oral administration in healthy humans. The oral bioavailability is 34%, and it can be reduced with the consumption of food. Specifically, the Cmax and AUC is reduced by an average of 70% and 61% with a low-fat meal, and 50% and 48% with a high-fat meal compared to the fasted state, an effect which is apparent up to six hours following food intake.
Betrixaban is reported to present mainly a gastrointestinal elimination route, it has been shown that even 85% of it gets disposed in the feces and only 11% of it can be found in the urine.
The apparent volume of distribution os 32 L/kg.
Betrixaban presents a minimal renal clearance (being 5-7% of the administered dose).

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Metabolism / Metabolites
One of the major characteristics of Betrixaban is its minimal hepatic metabolism (< 1%), preventing potential accumulation with liver impariment. Unchanged Betrixaban is the main form found in human plasma, followed by two hydolitic CYP-independent inactive metabolites (15-18%). The minimal hepatic metabolism produces an unlikely drug-to-drug interaction with inhibitors or agonists of CYP450.

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Biological Half-Life
Betrixaban presents a long half-life of between 19-27 hours.

Hepatotoxicity
In registration studies, serum aminotransferase elevations of greater than 3 times the upper limit of normal (ULN) occurred in 1% to 2% of betrixaban-treated patients and in a similar proportion of control subjects treated with enoxaparin. Similarly, aminotransferase levels rose to above 5 times ULN in 0.6% of betrixaban and 0.4% of enoxaparin treated control subjects. Aminotransferase elevations with jaundice arose in
Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Betrixaban is no longer marketed in the United States. Because no information is available on the use of betrixaban during breastfeeding and the drug is orally absorbable, an alternate drug is preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Betrixaban is reported to be present a proteing binding of about 60%.

[1]. Discovery of Betrixaban (PRT054021), N-(5-chloropyridin-2-yl)-2-(4-(N,N-dimethylcarbamimidoyl)benzamido)-5-methoxybenzamide, a highly potent, selective, and orally efficacious factor Xa inhibitor. Bioorg Med Chem Lett. 2009 Apr 15;19(8):21.

[2]. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013 Apr;19(4):446-51.

[3]. Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag. 2015 Jun 26;11:343-51.

Betrixaban is a secondary carboxamide obtained by formal condensation of the carboxy group of 4-(N,N-dimethylcarbamimidoyl)benzoic acid with the amino group of 2-amino-N-(5-chloropyridin-2-yl)-5-methoxybenzamide. A synthetic anticoagulant compound that targets activated factor Xa in the coagulation cascade. It has a role as an anticoagulant and an EC 3.4.21.6 (coagulation factor Xa) inhibitor. It is a member of guanidines, a member of benzamides, a secondary carboxamide, a monochloropyridine and a monomethoxybenzene.
Betrixaban is a non-vitamin K oral anticoagulant whose action is driven by the competitive and reversible inhibition of the factor Xa. It was selected among all lead compounds due to its low hERG channel affinity while sustaining its factor Xa inhibition capacity. Betrixaban, now developed by Portola Pharmaceuticals Inc., is prescribed as a venous thromboembolism (VTE) prophylactic for adult patients with moderate to severe restricted motility or with other risks for VTE. VTE can be manifested as deep vein thrombosis or pulmonary embolism and it is a leading cause of preventable death in hospitalized patients.
Betrixaban is a Factor Xa Inhibitor. The mechanism of action of betrixaban is as a Factor Xa Inhibitor.
Betrixaban is an oral anticoagulant and direct inhibitor of factor Xa which is used to decrease the risk of deep vein thrombosis and pulmonary embolus in patients hospitalized with an acute medical condition who are at high risk for venous thromboses. Betrixaban has been linked to a low rate of serum aminotransferase elevations during therapy but has not been linked to instances of clinically apparent liver injury.
Betrixaban is an orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Betrixaban is primarily excreted unchanged in the bile and has a half life of about 19 hours.

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Drug Indication
Betrixaban is indicated for prophylaxis of venous thromboembolism (VTE) in conditions of moderate to severe restricted mobility or in patients that qualify as in risk of VTE.
FDA Label
Prevention of venous thromboembolism
Prevention of venous thromboembolism

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Mechanism of Action
Betrixaban is a cofactor-independent direct inhibitor of the Factor Xa and inhibits free and prothrombinase-bound Factor Xa.

C23H22CLN5O3

451.91

451.141

330942-05-7

Betrixaban-d6;2098655-51-5;Betrixaban maleate;936539-80-9;Betrixaban hydrochloride;2099719-47-6

10275777

Light yellow to yellow solid powder

1.3±0.1 g/cm3

200-212 ºC

1.629

2.93

110.9

3

5

7

32

668

0

XHOLNRLADUSQLD-UHFFFAOYSA-N

InChI=1S/C23H22ClN5O3/c1-29(2)21(25)14-4-6-15(7-5-14)22(30)27-19-10-9-17(32-3)12-18(19)23(31)28-20-11-8-16(24)13-26-20/h4-13,25H,1-3H3,(H,27,30)(H,26,28,31)

N-(5-Chloropyridin-2-yl)-2-((4-(N,N-dimethylcarbamimidoyl)benzoyl)amino)-5- methoxybenzamide

PRT054021; PRT-021; MK-4448; MLN-1021; PRT 054021; PRT-054021; MK4448; MLN 1021; PRT 021; PRT021; MK 4448; MLN1021; trade name Bevyxxa

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (5.53 mM) (饱和度未知) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80+，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。