Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation.
BACKGROUND
Dabigatran is prescribed to increasing numbers of patients with atrial fibrillation (AF). Although routine monitoring is not considered to be useful, measuring drug concentrations can be clinically relevant in specific situations. The aim of this study was the comparison of different functional and non-functional assays for determination of dabigatran concentrations at different timepoints in a real-life patient population with AF. We focused on the differences between assays in identifying patients with low drug concentrations. Furthermore, we studied the effect of glucuronidation on the established concentration as determined with different assays.


METHODS
This study established dabigatran concentration ranges in 40 real-life AF patients by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) reference method and compared these with results from coagulation assays (Hemoclot dTT, LD-dTT and ECA). Samples were taken just before and 2 and 4 h after taking the drug.


RESULTS
A wide range of concentrations at different time points was found in this patient group. Coagulation assays correlate best with UPLC-MS/MS results that include the glucuronidated metabolites, showing that the pharmacologically active glucuronides are also measured in coagulation testing. The LD-dTT has the best agreement with UPLC-MS/MS and combines good sensitivity with high specificity. Several patients show consistently low or high drug concentrations, implying that drug exposure differs between patients.


CONCLUSIONS
Based on the association of dabigatran concentrations with bleeding and thromboembolic risk, we believe that dabigatran monitoring could be beneficial for further optimizing anticoagulation therapy in AF.
Kristel
K
Boonen
Ellen
E
Schmitz
Fleur
F
Rozestraten
Dennis
D
van den Heuvel
Luc
L
Brunsveld
Pepijn
P
van der Voort
Daan
D
van de Kerkhof
D000368:Aged; D000991:Antithrombins / Q000097:blood / Q000378:metabolism; D001281:Atrial Fibrillation / Q000097:blood* / Q000378:metabolism*; D000076103:Biological Variation, Individual; D001780:Blood Coagulation Tests; D002851:Chromatography, High Pressure Liquid; D000069604:Dabigatran / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry
D000991:Antithrombins; D000069604:Dabigatran
atrial fibrillation; blood coagulation test; dabigatran; hemorrhage; thromboembolism