The Pharmacokinetics of Apixaban in Patients With Cardioembolic Stroke in Acute Phase

Abstract

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.

Influence of <em>ABCB1</em> and <em>CYP3A5</em> gene polymorphisms on pharmacokinetics of apixaban in patients with atrial fibrillation and acute stroke

“…Peculiarities of pharmacokinetics are due to severity of the underlying disease, the concomitant pathology, and age of the patients; all these are reflected by CV% variability. 3 However, this reflects the actual clinical practice and the portrait of the average patient with a stroke; practicing doctors have to deal with this. Steady state concentration was not studied, but it could be more relevant for a pharmacogenetic study.…”

“…Thus, obtaining data on the pharmacokinetics of NOACs and the factors that affect it in patients with acute cardioembolic stroke helps develop algorithms for personalizing the choice and dosage of this group of drugs. Pharmacokinetics of apixaban in patients with acute stroke was studied earlier in the study by Kryukov et al 3 …”

Pharmacokinetics and Pharmacogenetics of Apixaban

“…По данным рандомизированного клинического исследования ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) у пациентов с неклапанной фибрилляцией предсердий (ФП) апиксабан в дозе 5 мг 2 р/д значительно снижал риск инсульта или системной эмболии на 21%, большого кровотечения на 31% и смерти на 11% по сравнению с варфарином [8,9]. Аналогичным образом, у пациентов с ФП, для которых терапия АВК оказалась неэффективной или считавшейся неподходящей, апиксабан снижал риск инсульта более чем на 50% по сравнению с АСК без значительного увеличения риска развития кровотечения, что убедительно продемонстрировало рандомизированное двойное слепое многонациональное исследование AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment) [10,11].…”