Abstract
Background : The aim of this study was to evaluate the safe and effective dose and blood concentration (BC) of bepridil. Methods : We measured BC by high-performance liquid chromatography (HPLC) in a total of 112 patients (80 male, mean age 64.3±12.5 years old) with arrhythmias who received oral bepridil therapy. BC was compared with the clinical features, ECG parameters, effectiveness on arrhythmias, and adverse events. Results : The mean dose of bepridil was 128±34mg/day and the mean BC was 751±462ng/ml. BC was significantly higher in patients who received 200mg/day than in those who received 100mg/day and 150mg/day (1,093±721ng/ml vs. 702±433ng/ml, p=0.02, vs. 759±408ng/ml, p=0.049) . During the mean follow up period of 899 days, sinus rhythm was maintained in 14 out of 109 patients with atrial tachyarrhythmias and 57 patients showed significant improvement in their symptoms. BCs were significantly higher in patients with symptomatic improvement than those without (866±541ng/ml vs. 622±329ng/ml, p=0.006) . BCs were also elevated in 10 patients with QTc interval>0.48 seconds and 6 patients with bradycardia < 50/min compared to those without these side effects (QTc prolongation : 1,086±471ng/ml vs. no side effects : 703±438ng/ml, p=0.005, Bradycardia : 1,056±522ng/ml vs. no side effects : 703±438ng/ml, p=0.03) . No patients have developed torsade de pointes or sudden cardiac death. Conclusions : It was considered that the appropriate dose of bepridil was less than or equal to 150mg/day for Japanese, and that the optimal BC, which brings about symptomatic improvement and fewer adverse events, was between 600 and 1,000ng/ml.
