Relationship Between the Plasma Level of Diphenylhydantoin Sodium and Its Cardiac Antiarrhythmic Effects

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Abstract
The effect of diphenylhydantoin sodium (DPH, Dilantin) on a variety of arrhythmias was studied in relation to its plasma levels. DPH was administered in one of three ways: (1) multiple intravenous doses, (2) single intravenous doses, and (3) oral doses. Ventricular arrhythmias occurring in many clinical conditions and atrial tachycardia, particularly if caused by digitalis excess, responded well to treatment with DPH. Three fourths of the responsive arrhythmias were abolished at plasma levels of DPH of 10 to 18 µg/ml. In most cases a critical, effective plasma level could be demonstrated; this level had to be exceeded in order to suppress the arrhythmia being treated. A method of rapidly effective oral therapy of arrhythmias with diphenylhydantoin is described, and a method of transition from intravenous to oral therapy is demonstrated. The antiarrhythmic action of diphenylhydantoin was accompanied by neither depression of sinoatrial nodal activity nor atrioventricular or intraventricular conduction disturbances, but was accompanied by a shortening of the Q-T interval. Hypotension accompanying the intravenous use of this drug was minimized by administration of the full dose in increments.