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(Circulation. 1968;38:363.)
© 1968 American Heart Association, Inc.

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

J. THOMAS BIGGER JR. M.D.¹; DONALD H. SCHMIDT M.D.¹; HENN KUTT M.D.¹

¹ From the Department of Medicine, College of Physicians and Surgeons, Columbia University; the Department of Neurology in Medicine, Cornell University Medical College; the Medical Service, Presbyterian Hospital of New York City; and the First (Columbia) Medical Division and the Second (Cornell) Neurology Service, Bellevue Hospital, New York, New York.

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.

Key Words: Digitalis • Electrical systole • Electrocardiographic effects • Intraventricular conduction

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