Investigation of the importance of CYP2D6 genotype in mesalazine metabolism

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Pamukkale Üniversitesi, Fen-Edebiyat Fakültesi, Biyoloji Bölümü, Türkiye

Tezin Onay Tarihi: 2022

Tezin Dili: Türkçe

Öğrenci: Melek Beste Özkan

Asıl Danışman (Eş Danışmanlı Tezler İçin): Alaattin Şen

Eş Danışman: Gürkan Semiz

Özet:

Mesalazine (5-aminosalicylic acid, 5-ASA) is a basic anti-inflammatory agent both used for the purpose of therapy and as a remission control in patients with enflammatory bowel diseases (EBD) such as ulcerative colitis and Crohn's disease. EBD patients use these anti-inflammatory drugs throughout their lives. Among the cytochrome P450 enzymes, the highly polymorphic enzymes most closely related to psychiatric drugs are the CYP2D6 enzymes. They are classified into ultra-rapid metabolizers, rapid metabolizers, normal metabolizers, and slow metabolizers based on their phenotypes. The metabolism status of CYP2D6 polymorphism influences its clinical outcome. While slow metabolizers are at risk of inadequate treatment, ultra-rapid metabolizers may experience toxicity. In this study, we investigated the relationship between CYP2D6 and 5-ASA based on the data obtained from the previous study conducted in our laboratory. The aim of this study is to investigate the effect of CYP2D6 on 5-ASA. At the same time, finding its metabolite, if any, and elucidating its kinetics, to bring new information to the literature was another purpose of this thesis. First of all, 5-ASA was dissolved with an appropriate solvent and the activity measurements were performed using the CYP2D6 enzyme. Then, HPLC-ESI-MS/MS analyzes was performed. Based the our results, Mesalazine appeared to have an inhibitory potential rather than being a substrate for the CYP2D6 enzyme. Based on the results from this research, when using mesalamine for a lifetime, the use of it with other drugs can lead to inadequate treatment or side effects in patients. The results of the study showed that when determining the drug dose in the clinic, a specific genotyping test should be routinely performed on the patient and the treatment should be regulated while considering the other drugs used by the patient. It is clear that the mentioned possible situations not only threaten the life of the patients, but also place a heavy burden on the health system.