Betrixaban

Activated blood coagulation factor X (FXa) plays a critical initiation step of the blood-coagulation pathway and is considered a desirable target for anticoagulant drug development. It is reversibly inhibited by nonvitamin K antagonist oral anticoagulants (NOACs) such as apixaban, betrixaban, edoxaban, and rivaroxaban. Thrombosis is extremely common and is one of the leading causes of death in developed countries. In previous studies, novel thiourea and oxime ether isosteviol derivatives as FXa inhibitors were designed through a combination of QSAR studies and molecular docking...

Venous thromboembolism (VTE), comprising deep-vein thrombosis (DVT) and pulmonary embolism (PE), stands as the third leading cause of vascular-related mortality on a global scale. Anticoagulation prophylaxis undeniably ensures a significant reduction in the risk of DVT, while simultaneously exposing individuals to an elevated likelihood of experiencing both major and minor bleeding events. Betrixaban is a novel oral anticoagulant, a direct factor Xa inhibitor, approved by the Food and Drug Administration (FDA) but not by the European Medicines Agency (EMA) for VTE thromboprophylaxis...

Venous thromboembolism (VTE) is a prevalent yet preventable cause of death, particularly among hospitalized patients. Studies have shown that the risk of VTE remains high for up to 6 months after discharge, highlighting the need for extended thromboprophylaxis as a viable treatment approach. Despite the availability of several anticoagulant drugs like vitamin K antagonists, heparinoids, rivaroxaban, apixaban, edoxaban, and dabigatran, none of them has received approval from the US Food and Drug Administration (FDA) for long-term thromboprophylaxis...

Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran. Although vitamin K antagonists (VKAs) have been traditionally used to prevent thromboembolic events, DOACs have gained popularity because of their faster onset and offset of action and reduced need for monitoring. This study aimed to provide more data for anticoagulants in patients with atrial fibrillation with bioprosthetic heart valves by incorporating all available trials to date...

Betrixaban Maleate, a novel oral, once-daily factor Xa inhibitor drug substance, was subjected to stress testing under a wide range of degradation conditions, including acidic hydrolysis, alkaline hydrolysis, oxidative, thermal, and photolytic, to determine its inherent stability. The drug was biodegradable in acidic and alkaline environments, and three new degradation products were identified. Two degraded products are formed in an acidic environment, while the third is in alkaline conditions. The three degradants were identified using UPLC-ESI/MS and isolated using mass-triggered preparative HPLC, and their structures were unambiguously elucidated using HRMS and 2 D NMR techniques...

BACKGROUND: Drug-induced liver injury (DILI) can be caused by any prescribed drug and is a significant reason for the withdrawal of newly launched drugs. Direct-acting oral anticoagulants (DOACs) are non-vitamin K-based antagonists recently introduced and increasingly used for various clinical conditions. A meta-analysis of 29 randomised controlled trials and 152116 patients reported no increased risk of DILI with DOACs. However, it is challenging to predict the risk factors for DILI in individual patients with exclusion of patients with pre-existing liver disease from these studies...

The SARS-CoV-2 main protease (Mpro ) is a crucial enzyme for viral replication and has been considered an attractive drug target for the treatment of COVID-19. In this study, virtual screening techniques and in vitro assays were combined to identify novel Mpro inhibitors starting from around 8000 FDA-approved drugs. The docking analysis highlighted 17 promising best hits , biologically characterized in terms of their Mpro inhibitory activity. Among them, 7 cephalosporins and the oral anticoagulant betrixaban were able to block the enzyme activity in the micromolar range with no cytotoxic effect at the highest concentration tested...

Cyclophosphamide (CP) is one of the most widely used anticancer drugs for various malignancies. However, its long-term use leads to ALDH1A1-mediated inactivation and subsequent resistance which necessitates the development of potential ALDH1A1 inhibitors. Currently, ALDH1A1 inhibitors from different chemical classes have been reported, but these failed to reach the market due to safety and efficacy problems. Developing a new treatment from the ground requires a huge amount of time, effort, and money, therefore it is worthwhile to improve CP efficacy by proposing better adjuvants as ALDH1A1 inhibitors...

A simple, rapid and eco-friendly method for synthesis of nitrogen and sulfur doped carbon dots (N,S-CDs) is described. The method involved one step carbonization assisted by a green microwave irradiation route using available and cheap sources, as sucrose (source for C) and thiourea (source for N and S). The formed aqueous solution of N,S-CDs showed excellent optical and electronic properties with high compatibility and stability. The particles of the prepared dots were spherical with a narrow range of size from 1...

Direct FXa inhibitors are an important class of bioactive molecules (rivaroxaban, apixaban, edoxaban, and betrixaban) applied for thromboprophylaxis in diverse cardiovascular pathologies. The interaction of active compounds with human serum albumin (HSA), the most abundant protein in blood plasma, is a key research area and provides crucial information about drugs' pharmacokinetics and pharmacodynamic properties. This research focuses on the study of the interactions between HSA and four commercially available direct oral FXa inhibitors, applying methodologies including steady-state and time-resolved fluorescence, isothermal titration calorimetry (ITC), and molecular dynamics...

In recent years, anticoagulant and antiplatelet use have increased over the past years for the prevention and treatment of several cardiovascular conditions. Due to the rising use of antithrombotic medications and the complexity of specific clinical cases requiring such therapies, bleeding remains the primary concern among patients using antithrombotics. Direct oral anticoagulants (DOACs) include rivaroxaban, apixaban, edoxaban, and betrixaban. Direct thrombin inhibitors (DTIs) include argatroban, bivalirudin, and dabigatran...

Direct oral anticoagulants (DOACs) represent a new generation of drugs that have been increasingly used in the prevention and treatment of thromboembolic states. According to the mechanism of anticoagulant action, DOACs are divided into two groups: direct inhibitors of thrombin (dabigatran) and direct inhibitors of activated factor X (FXa) (rivaroxaban, apixaban, edoxaban, betrixaban). Compared to the vitamin K antagonists, DOACs are superior in terms of onset of action, pharmacokinetic and pharmacodynamics properties and fixed daily dose without the need for routine coagulation monitoring...

The ADA (Age-D-dimer-Albumin) score was developed to identify hospitalized patients at an increased risk for thrombosis in the coronavirus infectious disease-19 (COVID-19) setting. The study aimed to validate the ADA score for predicting thrombosis in a non-COVID-19 medically ill population from the APEX trial. The APEX trial was a multinational, randomized trial that evaluated the efficacy and safety of betrixaban vs. enoxaparin among acutely ill hospitalized patients at risk for venous thromboembolism...

INTRODUCTION: The available oral anti-Xa agents are routinely used for the management of thrombotic disorders. A molecularly modified recombinant coagulation FXa, also known as Andexanet Alfa (AA), that has been developed as an antidote to neutralize the bleeding effects of oral FXa inhibitors, such as Apixaban and Rivaroxaban. MATERIALS AND METHODS: This study utilized thromboelastography (TEG 5000 Hemostasis System), to investigate the neutralizing effects of AA at different concentrations of oral FXa inhibitors measuring such parameters as R-Time, K-Time, Angle, and Max Amplitude (MA)...

Atraumatic splenic rupture (ASR) is a rare condition mostly associated with neoplastic, infectious, and inflammatory diseases. ASR associated with drug treatment is even rarer. In this case report, we highlight an unusual complication of the direct oral anticoagulant rivaroxaban. A 64-year-old male patient was admitted to the emergency department with complaints of faintness and diffuse abdominal cramps. The patient had no history of recent trauma. Clinical examination revealed hemodynamic instability with a moderate response to filling and mild abdominal discomfort on palpation...

BACKGROUND: Clinical trials provide conflicting evidence regarding oral factor Xa inhibitors for prevention of ischemic stroke in patients without a history of atrial fibrillation. METHODS: Critical appraisal of randomized clinical trials testing oral factor Xa inhibitors in patients without atrial fibrillation that reported ischemic stroke. RESULTS: Considering the 11 trials reporting >10 ischemic strokes during follow-up (97,578 participants, 1195 ischemic strokes), one tested apixaban (57 strokes), one betrixaban (52 strokes), and 9 rivaroxaban (1086 strokes)...

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients hospitalized for acute medical illnesses. Therefore, medical inpatients require a careful VTE and bleeding risk assessment to drive optimal strategies for VTE prevention. Low molecular weight heparin and fondaparinux have long been used for inhospital prophylaxis for patients at increased risk of VTE. The selection of patients who require post-discharge prophylaxis, and the role of direct oral anticoagulants remain debated...

Previous research has identified risk factors that may affect the risk of bleeding when individuals are exposed to oral anticoagulants. It is unclear if the risk continues to exist with the direct oral anticoagulants (DOAC). The purpose of this study was to assess the risk of bleeding in patients on DOACs (apixaban, rivaroxaban, dabigatran, edoxaban and betrixaban) based on known risk factors including demographics, medical conditions and concomitant medications. This study was a retrospective analysis using electronic health record (EHR) data from the University of Utah Hospital (Division of Cardiovascular Medicine) of individuals receiving a DOAC from 2015 to 2020...

Three eco-friendly spectrophotometric methods were developed for determination of the novel anticoagulant drug, betrixaban (BTX). The first method (method A) was based on direct analysis of BTX at 229.4 nm on the zero-order spectrum using methanol as the optimum solvent. While the second method (method B) was based on measuring difference absorption value (ΔA) of BTX at 335 nm, which was obtained from pH-induced spectral difference (difference spectra of BTX in 0.1 M NaOH versus 0.1 M HCl). The third method (method C) was based on measurement of the first-derivative amplitudes of BTX and its co-administered Ca channel blocker lercanidipine (LER) at 304 and 229 nm for simultaneous assay of BTX and LER, respectively...

Obesity is associated with cardiovascular complications such as diabetes and hypertension. However, obesity and high body mass index (BMI) can also be linked to improved clinical outcomes in certain patient populations. This counterintuitive observation is called the "obesity paradox." The effect of BMI on the risk of developing venous thromboembolism (VTE) in acutely ill medical patients remains unclear. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, acutely ill hospitalized medical patients were randomized to receive either extended-duration betrixaban or shorter-duration enoxaparin and followed for 77 days...