Antiarrhythmic Effects of a Lidocaine Congener, Tocainide, 2-amino-2',6'-propionoxylidide, in Man

Eight patients with frequent premature ventricular contractions (PVCs) were given single oral doses of 2-amino-2', 6'-propionoxylidide hydrochloride (APX), a lidocaine congener, to investigate the drug's efficacy, toxicity, and pharmacokinetics. Of the 7 patients receiving more than 100 mg, 5 demonstrated at least 60% reduction in PVCs in the 5-hour period following one of the doses; the responsiveness to APX was similar to that observed when intravenous lidocaine was given to the same patients. There were side effects of transient dizziness, lightheadedness, and nausea in 3 patients 20 to 30 min after doses of 400 to 800 mg; slightly smaller doses in 2 of these patients retained efficacy without side effects. There were no effects on arterial blood pressure, heart rate, or the electrocardiogram of normally conducted beats. Laboratory values remained within normal limits, although the hemoglobin level and hematocrit showed a small but significant fall probably related to repeated blood sampling during the study. Drug plasma levels at 1 and 2 hr after administration and the area under the plasma concentration-time curve were proportional to dose, and the drug disappeared with a mean elimination half-life of 14.7 +/- 1.7 hr (mean +/- SD). Plasma levels resulting in suppression of PVCs ranged from 1 to 5 mug/ml. A mean of 39.7 +/- 12.4% of an orally administered dose was recovered unchanged in 48-hr urine collections. Comparison of the present results with those previously obtained after intravenous administration of APX indicates that oral bioavailability of the drug was essentially complete. APX appears to be a promising orally effective antiarrhythmic drug with suitable pharmacokinetic characteristics to warrant studies designed to establish dosage regimens for chronic therapy.