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The Clinical Pharmacology of Propafenone
Author(s) -
SMITH NELLIS A.,
KATES ROBERT E.,
HARRISON DONALD C.
Publication year - 1987
Publication title -
journal of electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 0892-1059
DOI - 10.1111/j.1540-8167.1987.tb01443.x
Subject(s) - propafenone , medicine , pharmacology , supraventricular arrhythmia , antiarrhythmic agent , pharmacokinetics , plasma levels , oral administration , plasma concentration , oral dose , cardiology , heart disease , atrial fibrillation
Propafenone is a potent type Ic antiarrhythmic agent that has activity against a wide variety of supraventricular and ventricular arrhythmias. Clinical administration must be individualized, based on an appreciation of propafenone pharmacokinctics and dose‐response relationships, which are quite complex. Although a “therapeutic” plasma concentration is achieved in most patients with 300 mg orally every eight hours and plasma concentrations reach steady state after three days, marked interpatient differences in plasma concentrations occur. In addition, the effective plasma concentration required for arrhythmia suppression varies markedly in individual patients. Oral propafenone is subjected to a marked “first‐pass” hepatic elimination via a saturable oxidative pathway. This can result in a tenfold increase in plasma concentrations as the dose is increased from 150 to 450 mg. Accumulation of metabolites, notably 5‐OH propafenone, probably contributes to the net antiarrhythmic effect of oral propafenone during chronic oral administration. Propafenone may exacerbate ventricular arrhythmias in 20–15% of patients. This does not appear to be dose‐dependent, nor is it associated with a definite prolongation in QT interval.