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

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.