503612-47-3

Mechanisms of Action

Apixaban is an oral selective activated Xa factor inhibitor and can prevent thrombin generation and thrombosis.

Warnings and Precautions

Breastfeeding mothers should stop usage or stop breastfeeding. Use during pregnancy is not advised. Use while experiencing severe liver damage is not advised.

Description

Apixaban, marketed under the name Eliquis, is an innovative oral anticoagulant developed by Bristol Myers Squibb and Pfizer. It belongs to the class of Xa factor inhibitors and has demonstrated a high degree of potency, selectivity, and efficacy on factor Xa. The inhibition constants (Ki) for human factor Xa and rabbit factor Xa are 0.08 nM and 0.17 nM, respectively. In various clotting time assays using normal human plasma, apixaban exhibited concentrations (EC2x) required to double prothrombin time (PT), modified prothrombin time (MPT), activated partial thromboplastin time (APTT), and HepTest. It displayed the highest potency in human and rabbit plasma but less potency in rat and dog plasma in both PT and APTT assays.

Originator

Bristol Myers Squibb Company (United States)

Uses

Apixaban is a highly selective, reversible inhibitor of Factor Xa with Ki of 0.08 nM and 0.17 nM in human and rabbit, respectively. Clinical research demonstrated that apixaban, administered orally in 2.5mg dosages, had superior preventative effects against VTE following surgery compared to daily subdermal injections of 40mg enoxaparin. Notably, apixaban achieved this without an increased risk of bleeding. Eliquis, approved by the European Commission, is a direct inhibitor of factor Xa and was developed through a series of medicinal chemistry discoveries, starting with nonpeptide leads and involving rational drug design and optimization of drug-like properties. The synthesis of apixaban involves creating a bicyclic pyrazolo-pyridinone scaffold, and its discovery represents a culmination of innovative approaches in drug development.

Definition

ChEBI: A pyrazolopyridine that is 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide substituted at position 1 by a 4-methoxyphenyl group and at position 6 by a 4-(2-oxopiperidin-1-yl)phenyl group. It is used for the prevention and treatment of thromboembolic diseases.

Brand name

Eliquis

Clinical Use

Apixaban is an oral anticoagulant with highly selective inhibition of factor Xa. It was approved by the European Medicines Agency (EMA) for the treatment of venous thromboembolic events and first marketed in Germany under the brand name Eliquis in June 2011. Apixaban was co-developed by Bristol-Myers Squibb and Pfizer and represents the first approved drug for this indication since warfarin over 50 years ago.

in vitro

Apixaban demonstrated excellent pharmacokinetics with low clearance (CL: 0.02 L kg⁻¹h⁻¹) and a low volume of distribution (Vdss: 0.2 L/kg) in dogs. It showed a moderate half-life (t₁/₂: 5.8 hours) and good oral bioavailability (F: 58%). In various thrombosis models in rabbits, such as arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT), and electrically mediated carotid arterial thrombosis (ECAT), apixaban produced antithrombotic effects in a dose-dependent manner with EC50 values of 270 nM, 110 nM, and 70 nM, respectively. Additionally, apixaban significantly inhibited factor Xa activity in rabbit ex vivo with an IC50 of 0.22 μM. In chimpanzees, it showed a 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%).