The relation of the kinetics of pirmenol to its antiarrhythmic efficacy.

In a single-blind study the multiple oral dose kinetics of pirmenol were related to its efficacy in eight patients with frequent (mean, 631; range, 167-1374 beats/hour) premature ventricular contractions (PVC). Oral pirmenol was started at 100 mg bid for 48 hours and increased to 150 mg bid in six patients to obtain more than 70% suppression of PVC counts. Efficacy was achieved without side effects. Pirmenol decreased heart rate but not PR interval, QRS duration, or QTc interval. Peak plasma levels after the first 100-mg dose occurred at 1 to 3 hours and ranged from 0.6 to 1.9 micrograms/mL. Plasma elimination half-life ranged from 9.7 to 31 hours (mean, 18.3). From 67.4 to 171.3 mg pirmenol (mean, 102.3 mg) were recovered in the urine in 48 hours after the last dose. Cumulative excretion in divided urine collections was consistent with a mean elimination half-life of 15 to 20 hours. The pharmacokinetics of pirmenol support oral twice-daily administration. The minimum PVC suppressing plasma level is between 0.5 and 1.5 micrograms/mL.