IntroductionDifficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke.Patients and methodsPharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at −70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent.ResultsABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A.ConclusionQuestions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class.

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Aim. To study pharmacokinetics of apixaban in patients with atrial fibrillation and cardioembolic stroke in acute phase. Material and methods. 17 patients (14 women and 3 men), aged 76.6±9.5 years with atrial fibrillation and cardioembolic stroke in acute phase were enrolled into the study. High performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Results. Intake of a single dose of apixaban 5 mg is described by the following pharmacokinetic parameters: geometric mean of Cmax 124.5 ng/mL (CV%=48), AUC (0, τ) 1008.0 ng•h/mL (CV%=48), AUC (0, ∞) 2751.6 ng•h/mL (CV%=82), median Tmax 3 hours (min 1, max 4), mean t½ 16.9 h (SD 13.6). Negative correlation between NIHSS stroke severity score and Tmax was found (r=-0.628, p=0.007) as well as positive correlation between apixaban t½ and patient age (r=0.638, p=0.01). A tendency to increase in AUC (0, ∞) was observed according to CHA 2 DS 2 -VASc points amount but it did not reach the statistical significance (r=0.620, p=0.14). Conclusion. For the first time in Russia pharmacokinetic data of apixaban were obtained in patients with cardioembolic stroke in acute phase. It could be the basis for the development of new personalized approaches to anticoagulation therapy in these patients.