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GÜLÇEBİ İDRİZ OĞLU, MEDİNE

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GÜLÇEBİ İDRİZ OĞLU

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2011 - 20182
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Subject: ANTIEPILEPTIC DRUGS ×

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    The relationship between UGT1A4 polymorphism and serum concentration of lamotrigine in patients with epilepsy
    (ELSEVIER, 2011) ONAT, FİLİZ; Gulcebi, Medine Idrizoglu; Ozkaynakci, Aydan; Goren, Mehmet Zafer; Aker, Rezzan Gulhan; Ozkara, Cigdem; Onat, Filiz Yilmaz
    Lamotrigine (LTG) which has a widespread use in epilepsy treatment as an antiepileptic agent is metabolized by UDP-glucuronosyl transferase (UGT) enzymes. In this study, single nucleotide polymorphisms, P24T and L48V, of the UGT1A4 enzyme have been investigated in a Turkish population of patients with epilepsy (n=131) by comparing serum levels of LTG of wild type and polymorphic subjects. High performance liquid chromatography (HPLC) was used to measure serum concentrations of LTG. The P24T and L48V polymorphisms of the UGT1A4 enzyme were analyzed with a matrix assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry method. The frequencies of the heterozygous alleles for L48V or P24T polymorphisms were 22.4% and 3.8%, respectively. L48V polymorphism was found to decrease the serum concentration of LTG in patients on monotherapy or polytherapy. The LTG levels of non smoking monotherapy patients were 52% lower for the L48V polymorphism than for wild type alleles. Also the LTG levels were significantly lower for non smoking or smoking polymorphic alleles than for normal. The high frequency of the L48V polymorphism detected in the Turkish population indicates that LTG dose adjustments in patients with the UGT1A4 L48V polymorphic enzyme should be taken into account. (c) 2011 Elsevier B.V. All rights reserved.
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    The effect of serum levetiracetam concentrations on therapeutic response and IL1-beta concentration in patients with epilepsy
    (ELSEVIER SCIENCE BV, 2018-12) ONAT, FİLİZ; Gulcebi, Medine I.; Kendirli, Tansel; Turgan, Zehra Asik; Patsalos, Philip N.; Onat, Filiz Yilmaz
    Objective: Assessment of the relevance between serum drug concentration to its therapeutic response is a valid monitoring strategy for the clinical efficacy of antiepileptic drugs (AEDs). Levetiracetam (LEV) is a broad spectrum AED with a possible anti-inflammatory effect. We aimed to determine the relationship between LEV concentrations and its therapeutic response, and the effect of LEV on IL1-beta concentrations in patients with epilepsy. Methods: Patients on monotherapy (n = 7) or polytherapy (n = 15) with LEV for their seizures management were included. Blood samples of each patient were collected: just before LEV intake, 1 h, 2 h, 4 h and 8 h following the last dose. Serum LEV concentrations were measured by liquid chromatography mass spectrometry and IL1-beta concentrations by chemiluminescent immunometric assay. Concentration to dose (C/D) ratio values was used for analyses. LEV concentrations were compared between responders (<= 1 seizure/month) and non responders (> 1 seizure/month) and patients with or without adverse reactions. IL1-beta concentrations before and at 2 h following LEV ingestion were compared in order to detect the effect of the increase in serum LEV concentration on IL1-beta. Results: Although there was no change in LEV (C/D) ratio or LEV maximum concentration (Cmax)/D ratio of the responders and non-responders, the C/D ratio following 1 h of LEV intake (2.17 +/- 0.59 kg.day/L) and Cmax/D ratio (2.25 +/- 0.56 kg.day/L) in the patients with adverse effects was significantly higher than for the patients without adverse effects (1.09 +/- 0.12 kg.day/L and 1.49 +/- 0.14 kg.day/L respectively). A statistically significant decrease was found in the IL1-beta concentration to LEV (C/D) ratio with the increase in LEV concentration in patients on LEV monotherapy. Conclusion: The possible relationship between LEV Cmax and its therapeutic response or IL1-beta concentrations may be an importance indication of LEV antiepileptic efficacy. Consequently, monitoring LEV Cmax values may enhance LEV adherence because patients would be less likely to develop adverse effects.