Preventive Strategies against Bleeding due to Nonvitamin K Antagonist Oral Anticoagulants

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