title: Determination of the anti-F10a or anti-F2a generation action of rivaroxaban or dabigatran.
abstract: Dabigatran and rivaroxaban are new oral inhibitors of the thrombin (F2a) and F10a, respectively. Both inhibitors decrease the extrinsic or intrinsic generation of F10a/F2a in plasma. An innovative test for extrinsic F10a/F2a generation is the extrinsic coagulation activity assay (EXCA). With the EXCA the action of all F10a/F2a generation inhibitors can be quantified. The present work aimed to establish the mean therapeutic ranges of these two new drugs, as determined in the EXCA. Forty microlitres reconstituted lyophilized commercial pooled normal plasma, that had been supplemented with 0-0.48 mg/l dabigatran or rivaroxaban, in high-quality polystyrene U-wells (Brand781600), were incubated with 4 μl 1 ng/ml human placental tissue factor in 5% human albumin, 250 mmol/l CaCl2 (EXCA-trigger) for 1 min (EXCA-1) or 2 min (EXCA-2) at 37°C. 80 μl 2.5 mol/l arginine, 0.16% Triton X 100, pH 8.6, were added. After 3 min, 20 μl 1 mmol/l CHG-Ala-Arg-pNA in 1.25 mol/l arginine was added and ΔA/t was determined (37°C). The mean therapeutic range (10-20% EXCA) of dabigatran is approximately 0.05-0.1 mg/l. The mean therapeutic range (10-20% EXCA) of rivaroxaban is approximately 0.13-0.22 mg/l. Mean prophylactic concentrations (20-40% EXCA) are approximately 0.02-0.05 mg/l dabigatran and approximately 0.05-0.13 mg/l rivaroxaban. These are the mean ranges. Individual plasma might well behave differently: either an individual patient could be more sensible or more resistant towards one or both of these drugs. It is suggested to perform EXCA tests for each individual patient to determine the real drug dosage he needs to reach 10-20% of normal EXCA for therapy or 20-40% of normal EXCA for prophylaxis.
authors: Institute of Laboratory Medicine and Pathobiochemistry, University Hospital, Marburg, Germany. thstief@med.uni-marburg.de
authors: Thomas W
authors: TW
authors: Stief
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors*; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D009025:Morpholines; D013876:Thiophenes; D015091:beta-Alanine; D000069552:Rivaroxaban; D013917:Thrombin; D000069604:Dabigatran