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Summary of food and drug interactions with dabigatran.
Note: Reprinted with kind permission from the Springer Science and Business Media.21
Abbreviations: Tmax, time to maximum concentration; Cmax, maximum plasma concentration; AUC, area under the curve; P-gp, P-glycoprotein; AF, atrial fibrillation; CYP3A4, cytochrome P450 3A4; LMWH, low molecular weight heparin; NSAIDs, nonsteroidal anti-inflammatory drugs.

Summary of food and drug interactions with dabigatran. Note: Reprinted with kind permission from the Springer Science and Business Media.21 Abbreviations: Tmax, time to maximum concentration; Cmax, maximum plasma concentration; AUC, area under the curve; P-gp, P-glycoprotein; AF, atrial fibrillation; CYP3A4, cytochrome P450 3A4; LMWH, low molecular weight heparin; NSAIDs, nonsteroidal anti-inflammatory drugs.

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... Dabigatran etexilate and tartaric acid are the primary components of dabigatran. Dabigatran etexilate is absorbed at a low pH [26]; thus, a tartaric acid core is provided in dabigatran capsules [8]. Tartaric acid can create an acidic environment as it has pKa values of 2.98 and 4.34 [27]. ...
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Dabigatran is a novel oral anticoagulant that directly inhibits free and fibrin-bound thrombins and exerts rapid and predictable anticoagulant effects. While the use of this reagent has been associated with an increased risk of gastrointestinal bleeding, the reason why dabigatran use increases gastrointestinal bleeding risk remains unknown. We investigated the cytotoxicity of dabigatran etexilate and tartaric acid, the two primary components of dabigatran. The cytotoxicity of dabigatran etexilate and tartaric acid was measured in a cell viability assay. Intracellular mitochondrial reactive oxygen species (mitROS) production and lipid peroxidation were measured using fluorescence dyes. Cell membrane viscosity was measured using atomic force microscopy. The potential of ascorbic acid as an inhibitor of dabigatran cytotoxicity was also evaluated. The cytotoxicity of dabigatran etexilate was higher than that of tartaric acid. Dabigatran etexilate induced mitROS production and lipid peroxidation and altered the cell membrane viscosity. Ascorbic acid inhibited the cytotoxicity and mitROS production induced by dabigatran etexilate. Therefore, we attributed the cytotoxicity of dabigatran to dabigatran etexilate, and proposed that the cytotoxic effects of dabigatran etexilate are mediated via mitROS production. Additionally, we demonstrated that dabigatran cytotoxicity can be prevented via antioxidant treatment.
... So, penetration of dabigatran use might be limited in clinical practice. 35) The bleeding rate and ischemic event of apixaban was analyzed in AUGUSTUS study. This study enrolled the highest number of patients, 4,600 patients of ACS or PCI performed AF patients were randomized into the 2 by 2 factorial designed this study. ...
... Meanwhile, reports that anti-Xa activity or the level of prothrombin fragment 1 þ2 reflects the anticoagulation effects of apixaban or rivaroxaban have been presented recently, which might lead to the daily clinical application of these tests [12,13]. At present, diluted thrombin time or ecarin clotting time is reported to be useful in patients receiving dabigatran, but these might not be practical methods for use as high-specificity laboratory tests [14]. Simple methods for estimating the anticoagulation effects of NOACs at low cost are desirable in patients treated with NOACs. ...
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Background Little is known about physiological anticoagulation effects via antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral anticoagulants (NOACs). Methods We evaluated 120 consecutive patients with non-valvular atrial fibrillation (AF) receiving NOACs. Patients were randomly divided into three groups: a dabigatran group (DG, N=40), a rivaroxaban group (RG, N=40) or an apixaban group (AG, N=40). A warfarin group (WG, N=40) was matched with NOAC groups for age, sex and type of AF during the same time period. Blood samples were obtained in pretreatment, trough and peak phases to measure the activity of physiological coagulation inhibitors, including AT III and PC/PS or thrombus formation markers such as D-dimer and thrombin–antithrombin complex (TAT). Results D-dimer, TAT and AT III values for the NOAC groups were equivalent in the peak and trough phases. PC/PS activity in both phases was equally maintained in the pretreatment phase in the NOAC groups, while the activity in the WG was significantly suppressed in steady state. Moreover, no differences in trends for PC/PS activity were observed among NOAC groups. Conclusions PC/PS activity was constant in both peak and trough phases in the patients on NOACs compared with activity of those on warfarin. In addition, there was no difference in the findings among NOACs.
... En los ensayos clínicos de fases II y III en pacientes con FANV solo se evaluó el esquema de dosis fraccionado 29,30 , ya que, al contrario que en la profilaxis tras la cirugía, el objetivo en la FANV no sería tanto el inicio de acción rápido en las primeras h, como el mantenimiento del efecto anticoagulante a lo largo del tratamiento, preservando un perfil de seguridad y eficacia adecuados en el tiempo. Asumiendo que C máx se había relacionado con el riesgo de hemorragia, se consideró que el fraccionamiento de la dosis proporcionaría el mejor perfil de eficacia y seguridad, con disminución de la incidencia de eventos hemorrágicos asociada a la disminución del pico de C máx , manteniendo la eficacia anticoagulante en niveles clínicamente significativos a largo plazo. ...
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... Dabigatran etexilate is a small molecule that is rapidly absorbed after oral administration and converted into dabigatran acting directly by inhibiting thrombin, responsible for the conversion of fibrinogen into fibrin during coagulation cascade and preventing the development of thrombus (clot). In addition, dabigatran has proven its efficacy and safety without the need of coagulation monitoring and dose adjustments, and does not cause dietary restrictions for patients [8]. ...
... In the probabilistic analysis, 1000 simulations (Monte Carlo second order) were estimated for each perspective and for each outcome. Results were evaluated and ranked as follows: quadrant 1 (incremental effectiveness 4 0 and incremental cost 4 0), quadrant 2 (incremental effectiveness o 0 and incremental Source: RE-LY Steering Committee and Investigators [8,9]. * Used as second-line treatment. ...
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... Dabigatran etexilate is a prodrug for the direct thrombin inhibitor dabigatran. 3 Dabigatran binds to thrombin and inhibits the conversion of fi brinogen to fi brin. The drug has a desirable pharmacokinetic profi le with a rapid onset of action. ...
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During the last decade, non-vitamin K antagonist oral anticoagulants (NOACs) revolutionized the thromboprophylaxis management of several medical conditions, including atrial fibrillation and venous thromboembolism. Dabigatran etexilate was the first NOAC widely available worldwide, and it is currently the only one that directly inhibits thrombin. More recently, the availability of idarucizumab, a specific reversal agent, has increased the safety of dabigatran use in clinical practice, especially for those patients with severe and life-threatening bleeding. This review aims to summarize current evidence on dabigatran, starting from its pharmacological characteristics, and providing an updated overview of pivotal randomized controlled trials and real-world data on its efficacy and safety.
Article
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Article
The objective of this study was to find a new parameter to monitor bleeding tendency after dabigatran etexilate (Pradaxa) medication in Chinese nonvalvular atrial fibrillation patients. Blood samples of 231 nonvalvular atrial fibrillation patients were collected and five routine coagulation examinations (prothrombin time/International normalized ratio, activated partial thromboplastin time, fibrinogen assay, thrombin time and D-dimer) were assayed. After dabigatran etexilate administration, prolonged activated partial thromboplastin time and thrombin time were observed, especially TT. Derived parameter ΔTT (TT after dabigatran etexilate medication - TT before dabigatran etexilate medication) of bleeding patients was higher than nonbleeding patients (97.7 vs. 85.6 s, P = 0.038). When using ΔTT to distinguish patients with and without bleeding events, the cutoff value was 97.25 s, where sensitivity was 82.4% and specificity was 50.0%. The area under the curve was 0.786. TT is better than other routine coagulation parameters in monitoring the effect of dabigatran etexilate. ΔTT can distinguish bleeding patients from nonbleeding patients.