Table 1.
Summary of pharmacokinetic properties of nonvitamin K antagonist oral anticoagulants (NOACs) [22–25].
| Dabigatran | Rivaroxaban | Apixaban | |
|---|---|---|---|
| Target | Factor lla | Factor Xa | Factor Xa |
| Prodrug | Yes | No | No |
| Tmax (h) | 1.5–3.0 | 2.0–4.0 | 3.0–4.0 |
| Distribution volume (L) | 60–70 | ±50 | 23 |
| Half-life (h) | 11: healthy individuals 12-13: elderly |
5–9: healthy individuals 11–13: elderly |
8–15: healthy individuals |
| Bioavailability | 3–7% pH sensitive |
80–100%: 10 mg 66%: 15–20 mg under fasting conditions |
±50% |
| Protein binding | 35% | >90% | 87% |
| Metabolism | Conjugation | CYP-dependent and independent mechanism | CYP-dependent mechanism |
| Active metabolites | Yes glucuronide conjugates | No | No |
| Elimination | 80% renal | 33% unchanged via the kidney | 25% renal |
| 20% bile (glucuronide conjugation) | 66% metabolized in the liver into inactive metabolites then eliminated via the kidney or the colon in an approximate 50% ratio | 75% through the liver while the residue is excreted by the hepatobiliary route in the feces | |
| Effects of food | Tmax delayed; Cmax and AUC unchanged |
Tmax delayed; Cmax and AUC increased (76% and 30–40%, respectively) |
Tmax delayed; Cmax and AUC unchanged |
| CYP substrate | No | CYP3A4, CYP2J2 | CYP3A4 |
| P-gp substrate | DE: yes | Yes | Yes |