Psikiyatri hastalarında sitokrom P450 2D6 yavaş ve ultra hızlı metabolizör sıklıkları

Amaç: Sitokrom P450 (CYP206) birçok antipsikotik, antidepresan, bazı selektif serotonin gerialım inhibitörü, beta blokör, antiaritmik ilaçlar ve opiatların metabolizmasından sorumludur. Bu enzimin genetik polimorfizm gösterdiği ve buna bağlı olarak birçok ilacın metabolize edilme hızında bireyler ve toplumlararası farklılıkların bulunduğu bilinmektedir. Bu enzimin aktivitesine göre bireyler yavaş, orta, hızlı ve ultra hızlı olmak üzere dört alt gruba ayrılırlar. Bu çalışmada klinikte önem arz eden P450-2D6 enziminin psikiyatri polikliniğine başvuran hastalarda ultrahızlı ve yavaş metabolizörlerin belirlenmesi amaçlandı. Yöntem: Çalışma, Şubat 1999 ile Mart 2000 tarihleri arasında Gaziantep Üniversitesi Tıp Fakültesi Psikiyatri Polikliniği'ne başvuran hastalar üzerinde yapıldı. Hastaların tanıları DSM IV kriterlerine göre konuldu. Hastalardan 5cc EDTA'lı venöz kanları alındı. DNA'ları izole edildikten sonra PCR teknikleri kullanılarak P450-2D6 enzimi için ultra hızlı ve yavaş metabolizör olanlar tespit edildi. Bulgular: Çalışmaya 68 hasta katıldı. Hastaların yaş ortalaması 33,5±11,2 olup, 38'i erkek, 30'u kadın idi. Hasta grubunda CYP2D6 ultrahızlı bireylerin sayısı 7 (%10.29) idi. İlaç metabolizması bakımından tam yetersiz grup olan yavaş metabolizör hasta sayısı ise 1 (%l,45) idi. Sonuç: Bulgulara göre Türk hastalara sitokrom P450-2D6 enzimiyle metabolize edilen antipsikotik ve antidepresanlar veya bu enzimce melabolize edilen herhangi bir ilaç verildiğinde hastaların yaklaşık %10'unda etkili kan düzeyi elde edilemeyeceği ve %1-2 hastada kan düzeylerinin asırı yükselmesine bağlı olarak şiddetli yan etki görülmesi beklenebilir. Antipsikotik ve antidepresanların kullanılmasından önce bir bireyin P450-2D6 enzim aktivitesinin tayin edilmesi etki ve yan etkilerin öngörülebilmesi bakımından yararlı olacaktır.

The frequencies on poor and ultrarapid metabolizers of cytochrome P450 2D6 in psychiatric patients

Objective: The cytochrome P450-2D6 (CYP2D6) is involved in the metabolism of many antipsychotic medications such as tricylic antidepressants, some selective serotonin reuptake inhibitors and also beta-blockers, antiarrhythmic drugs and opiates. This enzyme shows genetic polymorphism. Therefore, the blood levels of drugs thad are metabolised by this enzyme may be different with respect 10 individuals and populatioııs. CYP2D6 has four metabolizer subgroups: deficient, intermediate, rapid, and ultrarapid in this study, our aim was to determine the frequencies of deficient (poor metabolizers) and ultrarapid groups which are important clinically. Method: This study was carried out on patients who attended the University of Gaziantep between February 1999 and March 2000. The diagnosis was strictly carried out according to the DSM IV criteria. 5 cc venous blood was taken from the patients. Af t e r the isolation of DNA, deficient and ultrarapid enzymes were determined by the PCR technique Results: Sixty-eight patients were included in the study. The average age of the patients was 33.5±11.2 ; 38 were male and 30 were female. Seven (10.29%) patients was diagnosed as ultrarapid and l (1.45%) as a poor metabolizer. Conclusion: Our results suggest that effective blood levels of drugs which are metabolized by P450-2D6 may not be achieved in approximately 10% of Turkish patients, and toxic concentrations or unusual psychotropic side effects may occur in 1-2%. Determining an individual's P450-2D6 genotype prior to antipsychotic and antidepressant therapy makes it possible to anticipate the effects and side effects of these drugs.

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