Direct Anticoagulant Properties

The direct oral anticoagulants have a rapid onset of anticoagulant activity, reaching peak anticoagulant effect within 0.5 to 4 h of ingestion.

Their half-lives are relatively short, much shorter than the pharmacodynamic effects of vitamin K antagonists.

In patients with normal renal function, the half-life of each direct oral anticoagulant can predict the duration of anticoagulant effect.

Prolonged anticoagulation occurs in patients with impaired renal function. The direct anticoagulants have variable renal clearance and short half-lives, averaging 12 h (Table 1).

 

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
80
Apixaban3~ 12AF: 171
VTE: 132
AF: 103
VTE: 63
27
Betrixaban3-419-2736*N/A11
Edoxaban1-210-14AF: 170
VTE: 234
AF: 36
VTE: 19
50
Rivaroxaban3-45-13AF: 246
VTE: 270
AF: 44
VTE: 26
67

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.

Drug-drug interactions, particularly with drugs that strongly inhibit the P-glycoprotein transporter and cytochrome P450 systems, can cause delayed clearance and elevated drug concentrations.