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

Eren Demirpolat; Mükerrem Betül; Gökhan Metan; Volkan Kahraman; Gökçe Şeker Karatoprak

Makale detayları

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

Yazarlar:

Eren Demirpolat | Mükerrem Betül | Gökhan Metan | Volkan Kahraman | Gökçe Şeker Karatoprak

Yayıncı:

Erciyes University

Ana Başlıklar:

Farmakogenomik

Dergi:

Sağlık Bilimleri Dergisi Vol.33 Issue 2, pp.182-189

Belge Tipi:

Makale

Yayın Tarihi:

7/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001322799

pISSN:

1018-3655

Anahtar kelimeler:

Özet:

 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 usingLCMSMS.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 patients 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.

 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 usingLCMSMS.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 patients 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.

 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 usingLCMSMS.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 patients 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.

 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 LCMSMS 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.

Makale detayları

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

Yazarlar:

Eren Demirpolat | Mükerrem Betül | Gökhan Metan | Volkan Kahraman | Gökçe Şeker Karatoprak

Yayıncı:

Erciyes University

Ana Başlıklar:

Farmakogenomik

Dergi:

Sağlık Bilimleri Dergisi Vol.33 Issue 2, pp.182-189

Belge Tipi:

Makale

Yayın Tarihi:

7/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001322799

pISSN:

1018-3655

Antifungal activity

genotyping

voriconazoleAntifungal aktivite

genotipleme

vorikonazol

Sayı

Makale detayları

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

Yazarlar: Eren Demirpolat | Mükerrem Betül | Gökhan Metan | Volkan Kahraman | Gökçe Şeker Karatoprak

Yayıncı: Erciyes University

Ana Başlıklar: Farmakogenomik

Dergi: Sağlık Bilimleri Dergisi Vol.33 Issue 2, pp.182-189

Belge Tipi: Makale

Yayın Tarihi: 7/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001322799

pISSN: 1018-3655

Antifungal activity

genotyping

voriconazoleAntifungal aktivite

genotipleme

vorikonazol

Sayı

Yazarlar:

Eren Demirpolat | Mükerrem Betül | Gökhan Metan | Volkan Kahraman | Gökçe Şeker Karatoprak

Yayıncı:

Erciyes University

Ana Başlıklar:

Farmakogenomik

Dergi:

Sağlık Bilimleri Dergisi Vol.33 Issue 2, pp.182-189

Belge Tipi:

Makale

Yayın Tarihi:

7/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001322799

pISSN:

1018-3655