The clinical efficacy of bepridil depends on its concentration in human plasma

Background and purpose)Bepridil hydrochloride has been used to treat atrial fibrillation (AF) and atrial flutter(AFL) . However the required concentration of bepridil in plasma (Cbep)has not been determined satisfactorily. We report a study involving three cases in which bepridil was used for treating AF/AFL and the results of monitoring the Cbep just before dosing.(Case)Case 1 : A 76‑ year‑old woman with paroxysmal atrial fibrillation(PAF)was administered bepridil at 100 mg/day orally. An electrocardiogram taken on day 9 signified atrial fibrillation when the Cbep was 249 ng/mL but changed to sinus rhythm on day 15. The Cbep rose to 506 ng/mL on day 18. Case 2 : A 71‑year‑ old man with PAF and AFL was administered bepridil at 200 mg/day orally. The Cbep rose to 450 ng/mL on day 8 and sinus rhythm was evident. The bepridil dose was then changed to 100 mg/day and the Cbep decreased to 300 ng/mL without evidence of AF and AFL on day 162. Case 3 : A 74‑ year‑old man with frequent PAF and AFL was administered bepridil at 200 mg/day orally. The Cbep rose to 725 ng/mL and clear sinus rhythm was evident but bepridil administration was stopped since the QT interval became dangerously prolonged. The dose of bepridil was restarted at 100 mg/day on day 10 and was changed to 50 mg/day on day 21. The Cbep was 300 ng/mL on day 40 and sinus rhythm was restored.(Discussion)The results described in this report suggest the clinical effect of bepridil for AF depends on the Cbep. Monitoring the Cbep of each patient is important for avoiding side effects causedby bepridil overdose. The results described in this report suggest that(1)the clin‑ ical effect of bepridil for AF depends on the Cbep ;(2)high concentrations of bepridil have side effects such as prolonging the QT interval as observed in the waveform on ECG ; (3)It is possible to take a long time to appear efficacy to start treatment with low dosing of bepridil. ;(4)Rapid efficacy requires starting treatment with 200 mg/day bepridil. ;(5)However it is important for keeping the safety to check the Cbep and ECG soon after the start of treatment when the dose is modified 5 to 7 days after starting treatment with high dose of bepridil. ;(6)Cbep is checked just before dosing that the timing is less an individual difference than another points.