Table 1 Pharmacokinetic properties of direct oral anticoagulants
From: Perioperative management of patients on direct oral anticoagulants
| Â | Dabigatran | Rivaroxaban | Apixaban | Edoxaban |
|---|---|---|---|---|
Target | Factor lla | Factor Xa | Factor Xa | Factor Xa |
Prodrug | Yes | No | No | No |
Tmax (h) | 1.0–3.0 | 2.0–4.0 | 3.0–4.0 | 1.0–2.0 |
Half-life (h) | 12-17 h | 5–9: healthy individuals 11–13: elderly | 8–15: healthy individuals | 10–14 |
Bioavailability | 3–7% pH sensitive | For 2.5 mg and 10 mg: 80–100% (fasting or fed) For 15-20 mg: 66%: (fasting) almost 100% (fed) | ± 50% | 62% |
Metabolism | Conjugation | CYP-dependent and independent mechanism | CYP-dependent mechanism (25%) | CYP-dependent (<5%) and independent mechanism (<10%) |
Active metabolites | Yes - acylglucuronides | No | No | Yes (<15%) |
Elimination of absorbed dose | 80% renal | 33% unchanged via the kidney | 27% renal | 50% renal |
| Â | 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 | 73% through the liver, the residue is excreted by the hepatobiliary route | 50% metabolism and biliary/intestinal excretion |
CYP substrate | No | CYP3A4, CYP2J2 | CYP3A4 | CYP3A4 (<5%) |
P-gp substrate | DE: Yes | Yes | Yes | Yes |
BRCP substrate | No | Yes | Yes | No |