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The effect of polymorphic metabolism enzymes on serum phenytoin level

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Abstract

Phenytoin has a widespread use in epilepsy treatment and is mainly metabolized by hepatic cytochrome P450 enzymes (CYP). We have investigated CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3 allelic variants in a Turkish population of patients on phenytoin therapy. Patients on phenytoin therapy (n = 102) for the prevention of epileptic seizures were included. Polymorphic alleles were analyzed by restriction fragment length polymorphism method. Serum concentrations of phenytoin were measured by fluorescence polarization immune assay method. The most frequent genotype was detected for CYP2C9 wild-type alleles (78.43 %), whereas CYP2C19*2/*2 (5.88 %) was the least frequent genotype group. According to the classification made with both enzyme polymorphisms, CYP2C9*1/*1-CYP2C19*1/*1 (G1: 41.17 %) genotype group was the most frequent whereas CYP2C9*1/*2-CYP2C19*1/*3 (G7: 0.98 %) was the least frequent one. The highest mean phenytoin level (27.95 ± 1.85 µg/ml) was detected in the G8 genotype group (CYP2C9*1/*3-CYP2C19*2/*3) and the G1 genotype group showed the lowest mean phenytoin level (7.43 ± 0.73 µg/ml). The mean serum concentration of phenytoin of the polymorphic patients with epilepsy was higher than that for the wild-type alleles both in the monotherapy and polytherapy patients. These results show the importance of the genetic polymorphism analysis of the main metabolizing enzyme groups of phenytoin for the dose adjustment.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, University of Marmara, Istanbul, Turkey

    Aydan Ozkaynakci, Medine Idrizoglu Gulcebi & Filiz Yilmaz Onat

  2. Department of Molecular Biology and Genetics, Faculty of Art and Science, University of Yüzyıl, Istanbul, Turkey

    Deniz Ergeç

  3. Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, University of Üsküdar, Istanbul, Turkey

    Korkut Ulucan

  4. Department of Neurosurgery, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey

    Mustafa Uzan

  5. Department of Neurology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey

    Cigdem Ozkara

  6. Department of Medical Genetics, School of Medicine, University of Marmara, Istanbul, Turkey

    Ilter Guney

Authors
  1. Aydan Ozkaynakci
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  2. Medine Idrizoglu Gulcebi
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  3. Deniz Ergeç
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  4. Korkut Ulucan
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  5. Mustafa Uzan
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  6. Cigdem Ozkara
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  7. Ilter Guney
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  8. Filiz Yilmaz Onat
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Corresponding author

Correspondence to Filiz Yilmaz Onat.

Additional information

A. Ozkaynakci and M. I. Gulcebi contributed to this study equally.

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Ozkaynakci, A., Gulcebi, M.I., Ergeç, D. et al. The effect of polymorphic metabolism enzymes on serum phenytoin level. Neurol Sci 36, 397–401 (2015). https://doi.org/10.1007/s10072-014-1961-8

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  • DOI: https://doi.org/10.1007/s10072-014-1961-8

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