Evaluation of the Citalopram levels on QTc Interval in Rats using with Radio-telemetry

Yıl 2022, Cilt: 44 Sayı: 5, 646 - 653, 29.09.2022

Nuşin Harmancı , Çiğdem Toprak , Zuhal Kaltuş , Semra Yiğitaslan , Başar Sırmagül

https://doi.org/10.20515/otd.1083900

Öz

Long QT syndrome is an arrhythmogenic disease characterized by prolonged QT interval. Citalopram (CIT) was reported to prolong QT interval dose-dependently. Omeprazole (OMP), inhibits CIT metabolizing enzyme CYP2C19, thereby increases serum concentrations which may increase the risk of QT prolongation. These are commonly co-prescribed and recent studies have raised the safety concerns about. We aimed to investigate the dose dependent effects of citalopram alone and in combination with OMP. Forty male, Sprague Dawley rats were divided into 5 groups (n=8). CIT (10 mg/kg or 30 mg/kg) was given for 2 weeks alone or in combination with OMP (100 mg/kg) starting from the 2nd week. ECG recordings and blood samples were collected. QT interval significantly increased in all groups compared to control. The plasma level of CIT in the CIT30 group was significantly higher than CIT10 group (p<0.01) and was significantly higher in the CIT10+OMP group than that of the CIT10 group (p<0.01). In treatment groups, the increase in plasma citalopram level correlated positively with the increase in QT (r=0.844, r2=0.713). It was determined that CIT caused prolongation of QT interval, the addition of OMP increased QT interval more, and these increases correlated positively with CIT plasma concentration. Therefore, it would be appropriate to routinely measure CIT plasma levels in addition to ECG, particularly in patients with additional risk factors for QT prolongation.

Anahtar Kelimeler

Citalopram, Electrocardiography, LongQTsyndrome, Radiotelemetry, Therapeutic drug monitoring

Destekleyen Kurum

Financial Support Supported by Eskisehir Osmangazi University Commission of Scientific Researches under the Project Number: 2018/51. Eskisehir/TURKEY

Proje Numarası

Project Number: 2018/51.

Teşekkür

We would like to thank to the Prof. Dr. Ertuğrul Çolak for his contributions to statistical analysis support on this study.

Sıçanlarda Sitalopram Düzeylerinin Qtc Aralığı Üzerine Etkilerinin Radyo-Telemetri Yöntemi ile Değerlendirilmesi

Öz

Uzun QT sendromu, senkop ve ani ölüme neden olabilen QT aralığında uzama ile karakterize aritmojenik bir hastalıktır. Seçici serotonin geri alım inhibitörü olan sitalopram (CIT), en çok reçete edilen antidepresanlardan biridir. CIT'nin doza bağlı olarak QT aralığını uzattığı bildirilmektedir. Bir proton pompası inhibitörü olan omeprazol (OMP), CIT metabolize edici enzim CYP2C19'u inhibe eder, böylece CIT'nin serum konsantrasyonunu artırır ve bu da QT uzaması riskini artırabilir. CIT ve OMP genellikle birlikte reçete edilir ve son çalışmalar CIT ile OMP'nin birlikte kullanılmasıyla ilgili güvenlik endişelerini ortaya çıkarmıştır. Bu çalışmanın amacı, sıçanlarda sitalopramın tek başına ve OMP ile kombinasyon halinde QT aralığı üzerine olan etkilerini doza bağlı olarak araştırmaktır. Kırk adet erkek, Sprague Dawley sıçan 5 gruba ayrıldı (n=8). CIT 10 mg/kg ve 30 mg/kg 2 hafta süreyle oral gavaj yoluyla verildi, 2. haftadan itibaren de iki gruba OMP (100 mg/kg) ile kombine olarak verildi. Kontrol grubu sadece serum fizyolojik aldı. Birinci haftanın ve ikinci haftanın sonunda EKG kayıtları yapıldı ve kan örnekleri alındı. QT aralığı tüm gruplarda kontrol grubuna göre anlamlı olarak arttı. CIT30 grubundaki ilaç plazma düzeyi, CIT10 grubundan önemli ölçüde daha yüksekti (p <0.01). CIT10 + OMP grubunda CIT10 grubuna göre anlamlı derecede yüksekti (p <0.01). Tedavi gruplarında, plazma sitalopram düzeyindeki artış, QT aralığındaki artışla pozitif korelasyon gösterdi (r = 0.844, r2 = 0.713). Sitalopramın sıçanlarda QT aralığının uzamasına neden olduğu, metabolizma inhibitörü OMP eklenmesinin ise ilaç plazma düzeyini daha da arttırdığı. dolayısıyla QT aralığını da daha fazla arttırdığı gösterildi. Ek olarak QT aralığındaki artışların CIT plazma düzeylerindeki artışlar ile pozitif korelasyon gösterdiği belirlendi. Bu nedenle, özellikle QT uzaması için ek risk faktörleri olan hastalarda EKG takibinin ve CIT plazma düzeylerinin rutin olarak ölçülmesinin uygun olacağı görüşündeyiz.

Anahtar Kelimeler

Elektrokardiyografi, radyotelemetri, sitalopram, terapötik ilaç düzeyi izlemi, uzun qt sendromu

Proje Numarası

Project Number: 2018/51.

Kaynakça

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