Table 1.

Clinical pharmacokinetics of novel oral anticoagulants and renal impairment

Characteristic	Dabigatran	Apixaban	Rivaroxaban	Edoxaban
Bioavailability, %	6	50	80	Approximately 62
Onset of effect, min	≤30	NA	≤30	30
Duration of effect, h	24–36	≥24	24	≤24
Tmax, h	1.0–2.0	3.0	2.5–4.0	1.0–2.0
Renal excretion, % of dose	85	27	36a	35
Protein binding, %	35	87	92–95	55
Elimination half-life by renal impairment,b h
Normal (CrCl>80 ml/min)	13.8	7.6	8.3	10–14
Mild (CrCl=50–79 ml/min)	16.6	7.3	8.7	8.6
Moderate (CrCl=30–49 ml/min)	18.7	17.6	9.0	9.4
Severe (CrCl<30 ml/min)	27.5	17.3	9.5	16.9
AUC0–∞ increase relative to renal impairment
Mild	1.5×	1.16×	1.5×	1.32×
Moderate	3.2×	1.29×	1.86×	1.74×
Severe	6.3×	1.44×	2.0×	1.72×
ESRD	Estimated 6×c	1.39×	2×d	1. 93×e

Data are from ref. 37. NA, not available; Tmax, time to maximum concentration; CrCl, creatinine clearance; AUC_0–∞, area under the concentration time curve 0–∞.

^aIn total, 66% renal excretion: 36% unchanged and 30% inactivated metabolites.

^bFor ESRD (CrCl≤15 ml/min), no data were available from pivotal trials of approved novel oral anticoagulants.

^cExposure was doubled in subjects with ESRD when receiving one third of the normal dose (50 mg dabigatran).

^dExposure in subjects with ESRD receiving 10 mg rivaroxaban was equivalent to that in healthy subjects receiving 20 mg rivaroxaban.

^ePatients undergoing peritoneal dialysis.