PP175. CYP2C9 AND CYP2C19 POLYMORPHISMS IN PATIENTS UNDER PHENYTOINTHERAPY
A.E. ÖZKAYNAKÇI1, D. Sevinç2 ,Ç. Özkara3, M. Uzan4, A. Koçer5, R. Aker1, K. Ulucan6, M.Z. Gören1, E. Küçükibrahimoğlu1, R. Bircan7, H.B. Özyurt8, A.İ. Güney9, F. Onat1 1 Marmara University Faculty of Medicine Department of Pharmacology and Clinical Pharmacology, Istanbul, Turkey, 2 Maltepe University, Faculty of Medicine Department of Medical Biology and Genetics, Istanbul, Turkey, 3 Istanbul University , Cerrahpaşa Faculty of Medicine, Department of Neurology, Istanbul, Turkey, 4 Istanbul University, Cerrahpaşa Faculty of Medicine, Department of Neurosurgery, Istanbul, Turkey, 5 Abant Izzet Baysal University, Düzce Faculty of Medicine Department of Neurology, Düzce, Turkey, 6 Marmara University Faculty of Dentistry, Basic Sciences, Medical Biology and Genetics, İstanbul, Turkey, 7 Marmara University Faculty of Medicine Department of Medical Biology, Istanbul, Turkey, 8 Kartal State Hospital, Department of Radiation Oncology, Istanbul, Turkey, 9 Marmara University Faculty of Medicine Department of Medical Genetics, Istanbul, Turkey. e-mail: aydanozkaynakci@yahoo.com
*Corresponding Author:
page: 126

Abstract

The hepatic enzymes CYP2C9 and CYP2C19 are responsible for the metabolism of numerous clinically important drugs such as phenytoin with a narrow therapeutic index. Phenytoin is mainly oxidized by CYP2C9 and to a minor extend by CYP2C19. Polymorphism of CYP2C9 and CYP2C19 has been reported previously. In our study, the frequency of CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3 allelic variants were examined in  a group of 72 Turkish epileptic patients who received  phenytoin . Genomic DNA was isolated from peripheral leukocytes using phenol-chloroform extraction procedure.

 The allelic variants were studied by polymerase chain reaction and restriction fragment length polymorphism. Plasma phenytoin concentrations were determined utilizing fluorescence polarization immunoassay (FPIA) on Abbott AxSYM system. The frequencies of CYP2C9 and CYP2C19 genotypes in the study group were found to be 26.6 %, 16.6 %, 18.6 %, 18.6 %, 16.6 %, 2.6 %, 1.3 %, 2.6 %, 2.6 %1.3, % for CYP2C9*1/*1-CYP2C19*1/*1, CYP2C9*1/*1-CYP2C19*1/*2,  CYP2C9*1/*1-CYP2C19*1/*3, CYP2C9*1/*1-CYP2C19*2/*3, CYP2C9*1/*2- CYP2C19*1/*1, CYP2C9*1/*2-CYP2C19*1/*2, CYP2C9*1/*2-CYP2C19*1/*3, CYP2C9*1/*3-CYP2C19*2/*3, CYP2C9*1/*3-CYP2C19*1/*3 and CYP2C9*1/*3- CYP2C19*1/*2 genotype groups respectively. The mean plasma phenytoin concentrations were 6.53 g/ml for CYP2C9*1/*1-CYP2C19*1/*1, 9.37 g/ml for CYP2C9*1/*1-CYP2C19*1/*2, 8.04 g/ml for CYP2C9*1/*1, CYP2C19*1/*3, for CYP2C9*1/*2- CYP2C19*1/*1, 14.8  g/ml for CYP2C9*1/*2-CYP2C19*1/*2, 16.2  g/ml for CYP2C9*1/*2-CYP2C19*1/*3, 27.9 g/ml for CYP2C9*1/*3-CYP2C19*2/*3,  10.0 g/ml for CYP2C9*1/*3-CYP2C19*1/*3 and 6.7 g/ml for CYP2C9*1/*3- CYP2C19*1/*2 genotype groups.

The results show that there is a strong correlation between CYP2C9 and CYP2C19 genotypes and phenytoin dose requirement. It is suggested that the CYP2C9 and CYP2C19 genotyping can be used routinely to obtain efficient phenytoin therapy.




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