Репозиторий Университета

© 2019 Elsevier B.V. A new sample extraction protocol was developed for pharmacokinetic studies of dabigatran with high-performance liquid chromatography separation - electrospray ionization time-of-flight mass spectrometry analysis. After protein precipitation with acetonitrile, free dabigatran and its metabolites are separated into water phase by water-dichloromethane liquid-liquid extraction to purify the sample from proteins and endogenous lipophilic compounds. Chromatographic separation was achieved on an Agilent Zorbax SB-CN column (150 × 4.6 mm, 5 µm)) using 0.1% aqueous solution of formic acid and acetonitrile (80:20) as the mobile phase. Agilent Zorbax SB-CN column was selected to improve sample resolution and to avoided early elution of dabigatran previously seen when using a C18 column. The extended calibration curve was constructed from 5 to 1000 ng/L while precision and accuracy were assessed at four levels across the linear dynamic ranges. Within-run precision was <5.6% and the between-run precision was <3.9%. The method accuracy ranged from 89.8% to 104.4%. The developed method was successfully applied to 30 patient samples to evaluate antithrombotic efficacy and anticoagulant activity of dabigatran following knee endoprosthesis surgery.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. An HPLC-MS/MS method for determining dabigatran in human blood serum was developed. Samples were prepared by precipitation of proteins using MeOH followed by centrifugation and dilution with deionized H2O. The developed method had a simple sample-preparation procedure, short analysis time, and wide analytical range (from 1 to 1,000 ng/mL). This method was suitable for routine bioanalytical studies, in particular, therapeutic drug monitoring.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. In the clinical practice a physician quite often is at a loss due to “freedom of choice” granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

© 2018 Stolichnaya Izdatelskaya Kompaniya. The article presents a clinical observation of the left atrial appendage thrombosis in a 51-year-old female patient with a paroxysmal form of nonvalvular atrial fibrillation which occurred despite long-term anticoagulant therapy with apixaban in a full dose (5 mg b.i.d.), and the patient's management. The patient was admitted with recurrent symptomatic paroxysm for more than 48 hours, because of which, in accordance with the recommendations, transesophageal echocardiography was performed before an emergency rhythm restoration. Thrombus in the left atrial appendage 0.5×1.03 cm in size was detected. It was decided to refrain from the immediate restoration of the rhythm due to the very high risk of thromboembolic complications. In connection with the categorical refusal of the patient from warfarin, it was decided to replace apixaban with another direct oral anticoagulant - dabigatran 150 mg bid for a period of 4 weeks followed by performing a control transesophageal echocardiographic study. As a result, no thrombus was found on control echocardiography. The particularity of this observation is concomitant hypertrophic cardiomyopathy and diabetes mellitus type 1 in this patient..

© 2018 Sychev et al. Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. Patients and methods: A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Results: Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Conclusion: Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.