New oral pharmacotherapeutic agents for venous thromboprophylaxis after total hip arthroplasty

Table 1 Target specific oral anticoagulant pharmacokinetics

	Dabigatran etexilate[17,32-36]	Rivaroxaban[19,27,39,40]	Apixaban[21,27,41,42]	Edoxaban[43-45]
Half Life (t1/2)	(1) Healthy subjects: 12-15 h (2) Mild renal impairment (50–80 mL/min) : 15 h (3) Moderate renal impairment (30-50 mL/min): 18 h (4) Severe renal impairment (15-30 mL/min): 27 h	(1) Healthy subjects: – 5-9 h (2) Elderly: 11-19 h (3) Mild to moderate hepatic impairment: 10.1-10.4 h (4) Mild renal impairment (50–79 mL/min): 8.7 h (5) Moderate renal impairment (30-49 mL/min): 9 h (6) Severe renal impairment (15-29 mL/min): 9.5 h	(1) 2.5 mg: 6.8 h (2) 5 mg: 15.2 h (3) 10 mg: 11.1 h	8.75-10.4 h
Distribution	Vd: 50-70 L	Vd: 50 L	Vd: 21 L	Vd: > 300 L
Protein binding	35%	92%-95%	87%	40%-59%
Metabolism	(1) Hepatic: dabigatran etexilate is hydrolyzed to dabigatran (active form). (2) Dabigatran undergoes hepatic glucouronidation to 4 active acyl glucuronides, each accounting for < 10% of total dabigatran in plasma.	Hepatic: oxidative metabolism via CYP3A4/5 and CYP2J2	Hepatic: mainly via CYP3A4/5 with minor contribution from CYP1A2, CYP2C8/9/19, and CYP2J2	Hepatic: minimal hepatic contribution from CYP3A4
Bioavailability	3%-7%	Dose dependent (absolute bioavailability) (1) 10 mg 80%-100% in fasted state (2) 20 mg approximately 66% in fasted state	50%	62%
Onset (TCmax)	1-6 h (1) Healthy subjects in fasted state–1 h (2) Healthy subjects following high fat meal–3 h (3) Subjects undergoing elective hip surgery–6 h	2-4 h	2.5 mg: 1.5 h 5 mg: 3.3 h 10 mg: 3-4 h	1-2 h
Excretion	80% renal clearance	(1) 66% renal clearance (36% unchanged and 30% as inactive metabolite); (2) 28% fecal excretion (7% unchanged and 21% as inactive metabolite)	(1) 27% renal clearance unchanged (2) 25% fecal excretion unchanged	49% renal clearance