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Yıl:2018; Cilt: 8; Sayı: 2>> Özet
Psikiyatride Güncel; 2018;8(2):121-129
Farmakokinetik Faz II etkileşimler ve klinik sonuçları
İE Ertek, N Yüksel
Gazi Üniversitesi, Ankara
İlaç metabolizmasında görev alan reaksiyonlar geleneksel olarak faz I veya faz II olarak sınıflandırılır. Klinik psikofarmakoloji literatüründe, ilaç eliminasyon yolu olarak faz II metabolik reaksiyonların önemine az vurgu yapılmıştır. Sitokrom P450 enzimlerine kıyasla, uridin difosfat glukroniltransferaz (UGT) yolağı hakkında daha az şey bilinmektedir. Ancak, yaygın kullanılan anksiyolitik, antidepresan, duygudurum düzenleyici ya da antipsikotik ilaçların birçoğu ağırlıklı olarak glukuronidasyon yolu ile elimine edilmektedir. Faz II reaksiyonları esas olarak konjugasyon işlemlerini içerir. Bunlar arasında glukuronid, sülfat, glisin ve glutatyon konjugasyonları ile asetilasyon ve metilasyon basamakları yer alır. Transferazlar olarak bilinen enzimlerin aracılık ettiği Faz II süreçleri, uygun bir kısmı bir koenzimden endojen veya eksojen substratlara bağlar. Glukuronid konjugasyonu faz II reaksiyonlarının en önemlisidir. UGT enzimleri çoğunlukla karaciğer ve intestinal sistem dokularının endoplasmik retikulumlarında bulunurlar. Bu enzimler birçok psikotrop ilacın metabolizmasında görev aldığından klinik psikofarmakololoji ve ilaç etkileşimleri açısından önem taşımaktadır.
Pharmacokınetic phase II interactions and clinical results
Reactions involved in drug metabolism are traditionally classified as phase I or phase II. In the clinical psychopharmacology literature, little emphasis has been placed on the importance of phase II metabolic reactions as the drug elimination pathway. Less is known about the uridine diphosphate glucuronyltransferase (UGT) pathway than the CYP P450 enzymes. However; most commonly used anxiolytic, antidepressant, mood stabilizing or antipsychotic drugs are predominantly eliminated by glucoronidation. Phase II reactions mainly involve conjugation processes. These include glucuronide, sulphate, glycine and glutathione conjugates, and acetylation and methylation steps. Phase II processes mediated by enzymes known as transferases bind a suitable moiety from a coenzyme to endogenous or exogenous substrates. Glucuronid conjugation is the most important of phase II reactions. UGT enzymes are often localized in the endoplasmic reticulum of liver and intestinal tract tissues. Since these enzymes are involved in the metabolism of many psychotropic drugs, they are important in terms of clinical psychopharmacology and drug interactions.

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