WHICH TOOL IS THE BEST GUIDE OPTIMIZE THE VORICONAZOLE DOSAGE: THERAPEUTIC DRUG MONITORING OR CYTOCHROME P450 POLYMORPHISM?

Öz

Voriconazole (VCZ) is the drug of choice for invasive aspergillosis (IA). However, narraow therapeutic range and variable pharmacokinetics can effect the success of the therapy. VCZ serum concentration is influenced by several factor including CYP450 polymorphisms primarily by CY2C19. Therapeutic drug monitoring (TDM) of VCZ is highly recommended to check adequate serum concentrations. Herein, we investigated the usefulness of detecting CYP450 polymorphism. Patients with hematological malignancies were included in the study.CYP450 polymorphisms which are responsible for metabolism of VCZ were investigated using RT-PCR. TDM of VCZ was peformed usingLC/MS/MS.11 patients were included in the study. Frequencies of CYP2C19 genotypes are 27% for intermediate metabolizer; 36% rapid metabolizer, 18% for ultra rapid metabolizer, 18% for normal metabolizer. Two patients experienced dose related side effects and one of these patient’s voriconazole blood concentration was supratherapeuticAlthough VCZ is the drug of choice for thetreatment of IA, the variabality of the pharmacokinetics can influence the success of therapy significantly. Therefore implementing the pharmacogenetic testing and therapeutic drug monitoring to clinical practice might help clinicians to provide improved care to patients and improve treatment outcomes.

Anahtar Kelimeler

• Antifungal activity
• genotyping
• voriconazole

HANGİ ARAÇ VORİKONAZOL DOZUNU OPTİMİZE ETMEK İÇİN EN İYİ REHBERDİR: TERAPÖTİK İLAÇ İZLEME Mİ YOKSA SİTOKROM P450 POLİMORFİZMİ Mİ?

Öz

Vorikonazol (VCZ) invazif asperjilloziste (IA) tedavi seçeneklerinden biridir. Bununla birlikte ilacın dar terapötik penceresi ve değişken farmakokinetiği tedavi başarısını etkilemektedir. VCZ kan konsantrasyonu kendisini metabolize eden CYP2C19 polimorfizmleri başta olmak üzere bazı faktörler tarafından etkilenmektedir. Terapötik ilaç izlemi (TDM) yeterli kan düzeyine ulaşılmasının kontrolünü sağlamaktadır. Bu çalışma kapsamında CYP450 polimorfizmlerinin saptanmasının faydasını araştırmayı hedefledik. Hematolojik malignitesi olan hastalar çalışmaya dahil edildi. VCZ’ nin metabolizmasından sorumluCYP450 polimorfizmleri RT-PCR ile ve TDM ise LC/MS/MS ile yapıldı. 11 hasta çalışmayı tamamlayabildi. CYP2C19 genotiplerinin dağılımı orta dereceli metabolizör için %27, hızlı metabolizör için %36, ultra hızlı metabolizör için %18, normal metabolizör için %18 şeklindeydi. İki hasta dozla ilişkili istenmeyen etkiler yaşadı ve bu hastalardan birinin VCZ kan konsantrasyonu supraterapötik düzeydeydi. VCZ IA’ da tedavi seçeneği arasında yer alsa da farmakokinetiğindeki belirgin değişiklik tedavisini etkilemektedir. Bu sebeple VCZ’ nin TDM ve RT-PCR gibi metodlar klinikteki hekimin hastalara daha iyi bir bakım sağlamasında yardımcı olabilir, hastanın tedavisi daha iyi hale getirilebilir.

Anahtar Kelimeler

• Antifungal aktivite
• genotipleme
• vorikonazol

Kaynakça

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