CYTOCHROME P450 (CYP2C9) ACTIVENESS, EVALUATED VIA LOSARTAN TEST, AS PREDICTION MARKER FOR THE WARFARIN TREATMENT DOSAGE CHOICE IN PATIENTS WITH DELAYED OUTCOMES AFTER HEART VALVES REPLACEMENT
https://doi.org/10.15829/1560-4071-2015-10-70-74
Abstract
Aim. To evaluate the influence of gene СYP2C9 activeness via losartan test on the warfarin dosage management in earlier and long-term post-operational periods.
Material and methods. Totally 33 patients included with artificial heart valves. All patients underwent assessment of genes carriage by polymorphic marker СYP2C9 by PCR after preparing of DNA from whole blood. The activeness of СYP2C9 was assessed with losartan concentration and its metabolite (E-3174) in urine after single intake of losartan 50 mg.
Results. The level of losartan and its active metabolite (E-3174) in urine was a prognostic marker determining therapeutic dose of warfarin in cardiac surgery patients in long-term post-operation period.
Conclusion. The СYP2C9 assessment by losartan concentration and E-3174 in“losartan test” might help to determine warfarin treatment dosage in delayed postoperational period that might improve the efficiency and safety of pharmacotherapy in valve prosthesis patients.
About the Authors
S. M. ArslanbekovaRussian Federation
D. A. Sychev
Russian Federation
K. B. Mirzaev
Russian Federation
R. E. Kazakov
Russian Federation
V. V. Smirnov
Russian Federation
N. M. Magomedova
Russian Federation
E. Z. Golukhova
Russian Federation
References
1. Yasar U, Forslund-Bergengren C, Tybring G et al. Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin. Pharmacol. 2002; 71: 89-98.
2. Joy MS, Dornbrook-Lavender K, Blaisdell J, et al. CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases. Clin Pharmacol. 2009; 65(9): 947-53.
3. Li Z, Wang G, Wang L, et al. Effects of the CYP2C9*13 allele on the pharmacokinetics of losartan in healthy male subjects. Xenobiotica. 2009; 39(10): 788-93.
4. Yin T, Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 — rationale and perspectives. Thromb. Res. 2007; 120(1): 1-10.
5. Lindh J, Holm L, Andersson M, et al. Influence of CYP2C9 genotype on warfarin dose requirements a systematic review and meta-analysis. Eur J Clin Pharmacol. 2009; 65(4): 365-75.
6. Sychev DA, Anikin GS, Belolipetskaya VG, et al. Clinical pharmacogenetics of angiotensin II receptor blockers: new perspectives of pharmacotherapy individualization. Cardiovascular Therapy and Prevention. 2006; 5(2): 100-5. Russian (Сычев Д.А., Аникин Г. С., Белолипецкая В. Г. и др. Клиническая фармакогенетика блокаторов рецепторов ангиотензина II: новые возможности индивидуализации фармакотерапии. Кардиоваскулярная терапия и профилактика. 2006; 5(2): 100-5).
7. Michaud V, Vanier M, Brouillette D, et al. Combination of Phenotype Assessments and CYP2C9-VKORC1 Polymorphisms in the Determination of Warfarin Dose Requirements in Heavily Medicated Patients. Clinical pharmacology & therapeutics. 2008; 83(5): 740-8.
Review
For citations:
Arslanbekova S.M., Sychev D.A., Mirzaev K.B., Kazakov R.E., Smirnov V.V., Magomedova N.M., Golukhova E.Z. CYTOCHROME P450 (CYP2C9) ACTIVENESS, EVALUATED VIA LOSARTAN TEST, AS PREDICTION MARKER FOR THE WARFARIN TREATMENT DOSAGE CHOICE IN PATIENTS WITH DELAYED OUTCOMES AFTER HEART VALVES REPLACEMENT. Russian Journal of Cardiology. 2015;(10):70-74. (In Russ.) https://doi.org/10.15829/1560-4071-2015-10-70-74