Enhanced elimination of dabigatran: Identifying the appropriate patient for the use of continuous venovenous hemodialysis instead of intermittent hemodialysis-A simulation analysis.
There are clinical situations where rapid elimination of dabigatran is beneficial. Intermittent hemodialysis (IHD) removes dabigatran effectively but is not always available and requires a hemodynamically stable patient. We therefore investigated the continuous venovenous hemodialysis (CVVHD) technique for its potency in the elimination of dabigatran. Based on pharmacometric characterization of dabigatran in IHD, we simulated a broad range of dialysis settings for CVVHD and then applied the model to specific clinical situations. Dialysis of 3 hours' duration with typical clinical settings (dialysate flow rate 50 mL/min; blood flow rate 150 mL/min) reduced dabigatran plasma concentration by 14-17% in addition to the patient body clearance. Extending dialysis duration to 8 or 16 hours for patients with severe renal dysfunction resulted in additional reductions from 26% up to 40%. When comparing with IHD for different endpoints (reaching 50% of initial dabigatran concentration, or nondetectability of dabigatran by the Hemoclot test), CVVHD did not reach comparable elimination rates. CVVHD is not fast enough to prepare for urgent interventions in patients with high bleeding risks. However, in situations where less hemodynamically stressful modalities seem indicated, CVVHD might be useful in moderately to severely renally impaired patients to accelerate dabigatran elimination.
Corporate Division Medicine, Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Karl-Heinz
KH
Liesenfeld
Corporate Division Medicine, TA Cardiology, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Fredrik
F
Gruenenfelder
The Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany.
Andreas
A
Clemens
D000368:Aged; D000991:Antithrombins / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D000069604:Dabigatran / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D006435:Renal Dialysis / Q000379:methods*
D000991:Antithrombins; D000069604:Dabigatran
dabigatran; elimination; hemodialysis