Effects of Bepridil, a New Antianginal Agent, on Ambulatory Electrocardiography in Human Volunteers

Abstract

We studied the effects of bepridil, a new antianginal agent, on the ambulatory electrocardiogram in seven human volunteers. The drug was administered in three sequential periods of 12 days separated by 24 days without treatment. Heart rate was not significantly altered at 200 mg/day, but fell from day 3 at 300 mg/day and from day 1 at 600 mg/day. Average fall in heart rate was approximately 8% at 300 mg/day and 11% at 600 mg/day (day 7). At 200 mg/day the peak plasma level was reached after 11 days of treatment (0.28 +/- 0.4 microgram/ml). At 300 mg/day, a plateau was reached on day 7 (0.44 +/- 0.04 micrograms/ml) and at 600 mg/day from day 8 (0.97 +/- 14 micrograms/ml). We found a highly significant relationship between blood concentration of bepridil and mean RR interval lengths over 24 h. The QTc interval was lengthened at all doses, but there was no significant correlation between plasma level and increase in QTc interval length.