Indications
Apixaban is prescribed for several therapeutic purposes. It is primarily indicated for the reduction of stroke risk and systemic embolism in patients with nonvalvular atrial fibrillation. Additionally, it is employed in the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) following hip or knee replacement surgeries. Furthermore, Apixaban is utilized in the treatment of DVT and PE, serving to decrease the risk of recurrence.
Pharmacodynamics
The pharmacodynamic profile of Apixaban is characterized by its selective inhibition of Factor Xa, both in its free and bound states, independent of antithrombin III. This inhibition extends to prothrombinase, effectively preventing thrombus formation. Through this mechanism, Apixaban contributes significantly to its anticoagulant effects, reducing the probability of clot-related events.
Absorption
Apixaban exhibits approximately 50% bioavailability, although certain studies suggest an oral bioavailability range of 43-46%. This parameter is crucial in understanding the extent to which the drug becomes available in the systemic circulation following oral administration, thus influencing its therapeutic efficacy.
Metabolism
Upon oral administration, about 50% of Apixaban is excreted unchanged, while 25% of the dose is eliminated as O-demethyl apixaban sulfate. Although the complete structure of all its metabolites is not fully defined, they account for approximately 32% of the excreted dose. Apixaban undergoes metabolism primarily via the cytochrome P450 3A4 (CYP3A4) enzyme system, with minor contributions from CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2J2 isoenzymes, which reflects its complex metabolic pathway.
Mechanism of Action
Apixaban functions as a selective inhibitor of factor Xa, effectively targeting this enzyme in both its free and bound states, independent of antithrombin III. Additionally, Apixaban inhibits prothrombinase. Through these mechanisms, it plays a critical role in preventing thrombus formation.
