Direct Oral Anticoagulant Plasma Concentrations

The predictable pharmacokinetics of the direct oral anticoagulants and their wide therapeutic window allow for standard fixed dosing without monitoring as with vitamin K antagonists. Mean peak and trough concentrations are shown in Table 1, but they are not targeted or validated levels. Consequently, specific monitoring of anticoagulant levels to optimize care has yet to be determined.


Table 1. Pharmacokinetic properties for direct oral anticoagulants.

Time to peak, hHalf-life, hPeak concentration, ng/mLTrough concentration, ng/mLRenal clearance, %
Dabigatran212-17AF: 175
VTE: 175
AF: 91
VTE: 60
Apixaban3~ 12AF: 171
VTE: 132
AF: 103
VTE: 63
Edoxaban1-210-14AF: 170
VTE: 234
AF: 36
VTE: 19
Rivaroxaban3-45-13AF: 246
VTE: 270
AF: 44
VTE: 26

Median plasma drug concentrations are derived from randomized clinical trials, with data from almost 30,000 patients randomized to a direct oral anticoagulant for stroke prevention in atrial fibrillation (AF) and 13,000 in the venous thromboembolism (VTE) trials. Patients were on full intensity dose unless they had decreased renal function.

* Dilute thrombin time, ecarin clotting time, or chromogenic direct thrombin assay, all with calibrations to determine dabigatran concentration.