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THE PHARMACOKINETICS OF APIXABAN IN PATIENTS WITH CARDIOEMBOLIC STROKE IN ACUTE PHASE

https://doi.org/10.20996/1819-6446-2016-12-3-253-259

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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 CHA2DS2-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. Keywords: new oral anticoagulants, apixaban, pharmacokinetics, atrial fibrillation, cardioembolic stroke

About the Authors

A. V. Kryukov
Russian Medical Academy of Postgraduate Education. Barrikadnaya ul. 2/1, Moscow, 123995, Russia
Russian Federation
MD, Post-Graduate student, Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Postgraduate Education


D. A. Sychev
Russian Medical Academy of Postgraduate Education. Barrikadnaya ul. 2/1, Moscow, 123995, Russia
Russian Federation
MD, PhD, Professor, Head of the Department of Clinical Pharmacology and Therapy; Leading Researcher, Group of Clinical Pharmacology Technologies, Research Centre of Russian Medical Academy of Postgraduate Education


D. A. Andreev
I.M. Sechenov First Moscow State Medical University. Trubetskaya ul. 8-2, Moscow, 119991, Russia
Russian Federation
MD, PhD, Professor, Department of Emergency Cardiology, I.M. Sechenov First Moscow State Medical University


A. V. Ryabova
Russian Medical Academy of Postgraduate Education. Barrikadnaya ul. 2/1, Moscow, 123995, Russia
Russian Federation
MD, Researcher, Group of Clinical Pharmacology Technologies, Research Centre of Russian Medical Academy of Postgraduate Education


N. P. Denisenko
Russian Medical Academy of Postgraduate Education. Barrikadnaya ul. 2/1, Moscow, 123995, Russia
Russian Federation
MD, Junior Researcher of the Group of Clinical Pharmacology Technologies


M. A. Loskutnikov
L.A. Vorohobov City Clinical Hospital № 67. Salama Adila ul. 2/44, Moscow, 123423, Russia
Russian Federation
MD, PhD, Head of Regional Vascular Center, L.A. Vorohobov City Clinical Hospital № 67


O. I. Vinogradov
N.I. Pirogov National Medical and Surgical Center. Nizhnyaya Pervomayskaya ul. 70, Moscow, 105203 Russia
Russian Federation
MD, PhD, Head of Neurovascular Department, N.I. Pirogov National Medical and Surgical Center


M. A. Domashenko
S.P. Botkin City Clinical Hospital. Vtoroy Botkinsky pr. 5, Moscow, 125284 Russia
Russian Federation
MD, PhD, Head of the Regional Vascular Center, S.P. Botkin City Clinical Hospital


References

1. National guidelines on the diagnosis and treatment of atrial fibrillation. Rossijskij Kardiologicheskij Zhurnal 2013; 4 (102) suppl 3: 3-100. In Russian (Национальные рекомендации по диагностике и лечению фибрилляции предсердий. Российский Кардиологический Журнал 2013; 4 (102) приложение 3: 3-100).

2. Shibazaki K., Kimura K., Aoki J. et al. Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation. J Neurol Sci 2013; 331 (1-2): 90-3.

3. Reilly P.A., Lehr T., Haertter S., et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RELY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 2014;63(4):321-8.

4. Cohen D. Dabigatran: how the drug company withheld important analyses. BMJ 2014 23;349:g4670.

5. Frost C., Wang J., Nepal S. et al. Apixaban, an oral, direct factor Xa inhibitor: single dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol 2013;75(2):476-87.

6. Doll DN, Barr TL, Simpkins JW. Cytokines: their role in stroke and potential use as biomarkers and therapeutic targets. Aging Disease 2014; 5 (5): 294-306.

7. House RV, Descotes J. Cytokines in human health immunotoxicology, pathology, and therapeutic applications. Totowa: Humana Press; 2007.


For citation:


Kryukov A.V., Sychev D.A., Andreev D.A., Ryabova A.V., Denisenko N.P., Loskutnikov M.A., Vinogradov O.I., Domashenko M.A. THE PHARMACOKINETICS OF APIXABAN IN PATIENTS WITH CARDIOEMBOLIC STROKE IN ACUTE PHASE. Rational Pharmacotherapy in Cardiology. 2016;12(3):253-259. https://doi.org/10.20996/1819-6446-2016-12-3-253-259

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)