[Effect of bepridil on the heart rate of the healthy subject. Correlation with plasma levels].

Bepridil, an antianginal agent similar in some of its properties to the calcium antagonists, causes a prolonged dose-dependent bradycardia in the dog. This study was undertaken to assess this effect in man. Seven volunteers were administered bepridil in 15 days' sequences separated by a three week interval. The doses were 200, 300 and 600 mg daily respectively. A 24 hour continuous ECG was recorded by the Holter method before each drug sequence and on the fifteenth days. The results were submitted for computerised analysis. The plasma concentrations of bepridil were measured on the 15th day before the ingestion of the morning dose, the half life of the product being about 3 days. After 15 days' therapy of bepridil 200 mg the plasma concentration was 0,23 +/- 0,04 microgram/ml and there was no change in heart rate. At the end of the 300 mg/day sequence, the plasma concentrations reached 0,39 +/- 0.07 microgram/ml and the heart rate fell significantly by 7,9 +/- 2,6%. After 600 mg daily; the mean plasma concentration was 0,82 +/- 0,10 microgram/ml and the fall in heart rate was 10,7 +/- 2,3%. There was an excellent correlation between the plasma concentration and the reduction in heart rate. This reduction is caused by an indirect effect decreasing the effects of adrenergic stimulation without apparent inhibition of the beta receptors and a direct effect decreasing the slope of diastolic depolarisation.