FERİDE GÖKBEN HIZLI SAYAR, Gül ERYILMAZ, EYLEM ÖZTEN, Işıl GÜL GÖĞCEGÖZ, MEHMET EMİN CEYLAN

Psikiyatride sitokrom P450 fenotiplemesinin kullanımı

Özellikle tedavisel aralığı dar olan ilaçlar için tedavi etkinliğini sağlayabilmek, yan etkileri en aza indirebilmek için farmakolojik tedavinin kişiye özel uygulanması gereklidir. Sitokrom P450 enzimlerinin fenotiplemesi hem değerli bir araştırma yöntemi, hem de metabolik kapasitesinin genetik temelinin değerlendirilmesi için bir araçtır. Teknik, bir prob ilaç (ölçüm maddesi) kullanarak metabolik kapasitenin tahmin edilmesine dayanır. Fenotipleme ilaç etkileşimleri, genetik polimorfizmler, hepatik hastalıklar ve ilacın farmakokinetiğini etkileyebilecek diğer etkenlerin toplam etkisini gösterir. Bunun için fenotiplemede her bir sitokrom enzim sistemine özgü substratların kullanımı gereklidir. Son dönemde birden fazla sitokrom enzim sisteminin in vivo değerlendirmesine olanak tanıyan ölçüm maddeleri kokteylleri ile fenotipleme kullanılmaya başlanmıştır.

The use of cytochrome P450 phenotyping in psychiatry

Individualization of pharmacotherapy is essential in order to optimize efficacy and minimize toxicity, especially for compounds with narrow therapeutic index. Cytochrome P450 phenotyping has been a valuable research tool and a way of assessing the genetic basis of metabolic capacity. Technique depends on estimating metabolic capacity based on conclusions drawn from another probe drug. Phenotyping allows estimation of the total influence of drug interactions, genetic polymorphisms, hepatic diseases and other factors altering pharmacokinetics. This requires the use of selective substrates for specific cytochrome enzymes. Recently some phenotyping methods are becoming widely used especially for the in vivo evaluation of multiple cytochrome enzymes by using probe cocktails.

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