Berberine of apixaban is comparable to rivaroxaban including half life, oral bioavailability, and metabolism. However, only 25% of apixaban is excreted in urine, compared with 66% of rivaroxaban. In terms of drug development, apixaban has limited supportive information from clinical trials to obtain an approval for VTE treatment and stroke prevention in patients with atrial fibrillation. Apixaban was only approved in Europe for the prevention of VTE after elective hip or knee replacement.35 Dabigatran Etexilate Background Dabigatran etexilate is an orally active prodrug of the active compound dabigatran that is similar to its predecessor ximelagatran. Dabigatran etexilate is a potent, reversible direct competitive inhibitor against factor IIa. Pharmacodynamics Dabigatran is a direct thrombin inhibitor that selectively, competitively, and reversibly inhibits both fibrin bound thrombin and free thrombin.39 Conversely, indirect thrombin research chemicals library inhibitors such as unfractionated heparin and LMWH cannot inhibit fibrin bound thrombin. Therefore, dabigatran has a unique ability to inhibit fibrin bound thrombin which theoretically benefits in terms of inhibiting coagulation cascade because fibrin bound thrombin can continue to trigger thrombin expansion.40 Pharmacokinetics Dabigatran etexilate is available in capsule form.
An active compound of dabigatran etexilate is coated with rhein tartaric acid to reduce the variability of dabigatran etexilate absorption, which markedly depends on an acid environment in the stomach. Therefore, it is recommended that the capsules should not be opened, crushed, or chewed because the bioavailability can increase up to 75%. This coated composition is in the form of tiny pallets. This form of administration allows dabigatran etexilate to be absorbed independently of the acidic environment in stomach and is not essentially disturbed by coadministration of a proton pump inhibitor.41 After oral administration, dabigatran etexilate is quickly absorbed and completely hydrolyzed to its active metabolite, dabigatran, by nonspecific ubiquitous esterases in the gut, plasma, and liver.42 The bioconversion begins in the gastrointestinal tract, thus the drug was absorbed in the portal vein as a combination of both prodrug and active moiety. The absolute bioavailability after oral administration of dabigatran etexilate ranges from 3% to 7%.43 After oral sirolimus administration of dabigatran, the time taken to reach the peak concentration level in the plasma is approximately 0.5 to 2 hours.
Steady state dabigatran concentrations are achieved within approximately 3 days in healthy volunteers and there is no unexpected accumulation of dabigatran after multiple dosing.41 In terms of metabolism, the bioconversion of dabigatran etexilate to active moiety is completed in the liver, and approximately 20% is conjugated with glucuronic acid and excreted via the biliary system.42 As dabigatran is approximately 35% protein bound, interactions involving protein binding are notthought to be clinically relevant.39 Dabigatran etexilate is not metabolized by the cytochrome P450 enzymes or other oxidoreductases but is a substrate for p glycoprotein. In patients with mild liver dysfunction, the AUC is comparable to that of healthy volunteers, and the bioconversion.