Serum Procainamide Levels As Therapeutic Guides

Abstract

Dosage schedules of procainamide should be individualised, because the amount of the drug required to control ventricular tachyarrhythmias varies widely among patients. Individual differences in procainamide pharmacokinetics are responsible for most of this variation and are reflected by the serum concentration of the drug. Procainamide concentrations in serum and in myocardial interstitial fluid must equilibrate rapidly and be similar at equilibrium. The effects of the drug on the myocardial cell membrane are proportional to the concentration at that site, develop quickly and are readily reversible. Accordingly, there is a useful relation between the serum concentration and the intensity of cardiac action of procainamide. Procainamide serum levels are most helpful for adjusting dosage schedules in patients whose response to the drug is difficult to evaluate or appears to be abnormal. Serum concentrations of 4 to 10mg/litre correct and prevent over 90 % of ventricular tachyarrhythmias responsive to procainamide without causing important adverse effects. Lower concentrations are partially effective in some patients. Additional therapeutic benefit is rarely obtained by raising the serum level above 10mg/litre, and serious toxicity becomes increasingly common above 12mg/litre. Serum concentration information must always be interpreted in the light of all other clinical information, since the type of arrhythmia and many other factors influence the response of the heart to procainamide. N-Acetylprocainamide, a metabolite of procainamide, possess antiarrhythmic activity and is not measured by the usual methods for determining serum procainamide. The concentration ratio of drug and metabolite in serum varies greatly among patients, and their potency ratio against various ventricular dysrhythmias in man remains in question. By measuring N-acetylprocainamide as well as procainamide, it may ultimately be possible to define a therapeutic range of the sum of the appropriately weighted concentrations of the 2 compounds. For the present, the therapist must rely primarily on the serum concentration of procainamide for supplementing his clinical judgment.