Pirmenol is a new orally effective antiarrhythmic agent. Reported are the results of oral administration of pirmenol to six patients (age 48.5 +/- 8.6 years, weight 83 +/- 15 kg) with stable ventricular extrasystoles (PVCs)--average ectopy rate 1040 +/- 630/hr (mean +/- SD). Patients received oral doses of placebo or 200 mg of pirmenol in a double-blind cross-over fashion followed by a single-blind rising-dose administration of 250 mg and 300 mg of pirmenol. The time period between doses was 48 hours. Pirmenol was rapidly absorbed (time to peak plasma levels 1 to 1.5 hours) and the mean maximum plasma concentrations were 1.8, 2.7 and 3.4 micrograms/mL with 200-mg, 250-mg and 300-mg doses, respectively. The elimination half-life was 9.3 +/- 3.0 hours and 31 +/- 14% of the dose was recovered in urine. The response criterion (80% suppression of PVCs of control for 8 hours) was met after the 300-mg dose in three patients. In three patients greater than 80% reduction occurred for up to 8 hours after the 200-mg dose. Pirmenol administration was not associated with any significant changes in blood pressure, heart rate, hepatic and renal function, PR interval or QRS duration. LV ejection fraction determined echocardiographically decreased from 63.0 +/- 6.9% predose to 59.7 +/- 5.0% about 2 hours after the 300-mg dose and QT interval increased by less than 10%. Two patients complained of transient bad taste sensation. Our results suggest that 250 mg to 300 mg of pirmenol, administered twice a day will suppress the PVCs effectively.