The Impact of Cyp4f2 Polymorphism on The Safety Profile And Regime Dosing of Phenindion In Patients With Valvular Atrial Fibrillation

Abstract

e24 Volume 37 Number 8S The ImpaCT of Cyp4f2 polymorphISm oN The SafeTy profIle aNd regIme doSINg of pheNINdIoN IN paTIeNTS WITh ValVular aTrIal fIbrIllaTIoN V.S. Shakhidzhanova; D.A. Sychev; R.E. Kazаkov; N.D. Grishenko; Y.Y. Palamarchuk; A.V. Kossovskaya; and A.Y. Tretyakov I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia Federation, Moscow, Russia; Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia Federation, Moscow, Russia; Federal State Institution “Scientific Centre of Medical Products Expertise”, Moscow, Russia; and Belgorod National Research University, medical faculty, Belgorod, Russia Introduction: In the reason of FDA prohibition in using of “new” oral anticoagulants, vitamin K antagonists have become uncontested drugs to the patients with valvular atrial fibrillation. The derivatives of indandion, as fluindione and phenindion, can be used in the case of intolerance and coumarins resistance. The role of the main genetic factors in individual sensitivity to coumarin’s anticoagulants is well known. But the influence of gen’s polymorphism CYP4F2 on the safety profile and regime dosing of phenindion haven’t been studied yet. Materials and Methods: Forty-two patients (20 male and 22 female), aged 27 to 80 years, valvular AF, were studied. The using of coumarin anticoagulants was impossible in all of them. All patients received phenindion in the dose of 30 to 130 mg daily with a target international normalized ratio (INR) of 2.0 to 3.0. Genotyping for polymorphism’s marker V433M gen CYP4F2 were designed using the PCR and RFLP (restriction fragment length polymorphism). Statistics were performed by Fisher’s exact tests. Results: Genotype CC was found in 26 patients (62%), genotype CT in 16 patients (38%), genotype TT wasn’t found at all. In the CC group (n = 26) high dose of phenindion (> 90 mg) was needed only in 2 patients (8%), versus 6 patients (37.5%) in the CT group (n = 16), P = 0.04 (significant statistically). In the CC group bleedings were found in 4 patients (9%) and in 1 patient (7%) in CT group, P = 0.63. In the CC group INR increased > 3.0 in 3 patients (8%). In the CT group nobody had INR > 3.0 (P = 0.5). Conclusion: The patients with genotype CT (polymorphism V433M gen CYP4F2) are usually needed in high dose of phenindion (> 90 mg) to achieve target INR of 2.0 to 3.0. There was not found out the influence of gen CYP4F2 polymorphism on the developing of bleedings and excessive hypocoagulation.