Abstract 13303: Effective Elimination of Dabigatran with Haemodialysis: A Phase I Single Centre Study in Patients with End-Stage Renal Disease
Dabigatran etexilate (DE) is the pro-drug of dabigatran (D), a synthetic low molecular weight orally active reversible direct thrombin inhibitor. DE is approved for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the primary prevention of thromboembolic events in the orthopaedic setting. A specific antidote for D has been recently preclinically identified and is therefore not yet available for clinical use in patients. Haemodialysis may be a measure in emergency situations requiring fast elimination of D. Dialysis modalities (catheter setting, blood flow rate of 200 ml/min, dialysate flow rate of 700 ml/min) are thought to apply for the majority of patients anticoagulated with DE and having a normal renal function. Six patients with end-stage renal disease (ESRD) received DE once daily over 3 days to achieve steady state (Day 1: 150 mg; Day 2: 110 mg; Day 3: 75 mg). Plasma trough concentrations at Day 3 were 146±58.1 ng/ml and increased to peak concentrations of 176±60 ng/ml 2 hours following the final dose of 75 mg. Dialysis was started 8 hours following the last dose to await absorption and distribution of the drug (D=150±58.9 ng/ml). After the 4-hour dialysis, plasma concentrations had dropped sharply to approximately one half (76±48 ng/ml). The extraction ratio calculated from blood entering and leaving the dialyser was 81.3±2.0%. The rebound after stopping dialysis was minor representing a 10% increase in plasma concentration.
Conclusions: The high dialysis extraction ratio of 81.3% in patients with ESRD and the minor rebound of plasma concentration after dialysis indicate that haemodialysis is an efficient method to remove D from the body. Four-hour dialysis under normal blood flow conditions eliminated about 50% of D. Elimination rates with a high blood flow rate of 400 ml/min will additionally be reported in an updated version of this abstract. Haemodialysis can be employed as an effective measure to eliminate D in emergency situations.
- © 2011 by American Heart Association, Inc.