Table 1.

Clinical pharmacology of novel oral anticoagulants

	Dabigatran[32]	Rivaroxaban[33]	Apixaban[34]	Edoxaban
Target of inhibition	IIa (thrombin)	Xa	Xa	Xa
Prodrug	Yes	No	No	No
Bioavailability, %	3–7	~66a	~50	62 [35]
Time to Cmax, h	1–2	2–4	3–4	1–2 [35,36]
Protein binding, %	35	>90	87	40–59 [36]
Substrate of P-gp drug transporter	Yes	Yes	Yes	Yes [37,38]
CYP metabolism, %	0	32	~25	Insignificantb[39]
Half-life, h	12–17	5–13c	~12	6–11d[36]
Renal elimination, % of total clearance	80	36 [40]	27	49 [35]
Drug interactions (examples)e	Strong P-gp inducers (e.g. rifampin) and inhibitors (e.g. dronedarone)	Combined P-gp and strong CYP3A4 inducers (e.g. carbamazepine) and combined P-gp and strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole)f	Strong inducers of both P-gp and CYP3A4 (e.g. rifampin) and strong inhibitors of both P-gp and CYP3A4 (e.g. ketoconazole)	Strong P-gp inhibitors (e.g. verapamil, quinidine) [38,41]

^aBioavailability of 66% in the fasted state for 20 mg dose, >66% if administered with food. ^bMetabolites M6 and M8 are formed through CYP3A, which accounts for <4% of parent exposure. Therefore, CYP enzymes appear to have an insignificant role in the metabolism of edoxaban [39]. ^cFive to 9 h in healthy patients aged 20–45 years, 11–13 h in elderly patients. ^dSix to 11 h for single doses of 10–150 mg, 9–10 h for multiple doses of 60–120 mg daily [36]. ^ePotential drug interactions that are to be avoided or may possibly require dose adjustments (not all examples are listed; see prescribing information for full details). ^fRivaroxaban exposure may be increased in patients with renal impairment taking P-gp and weak-to-moderate CYP3A4 inhibitors (e.g. amiodarone, diltiazem, and azithromycin).

Abbreviations: C_max maximum concentration of drug, CYP cytochrome P450, P-gp P-glycoprotein.