Cumulation of N‐acetylprocainamide, an active metabolite of procainamide, in patients with impaired renal function

Abstract
N-Acetylprocainamide (NAPA) accumulated in the plasma of 6 cardiac patients with renal failure taking procainamide chronically for therapy (4 were undergoing hemodialysis) and contributed to the therapeutic and toxic effects of the procainamide. NAPA plasma levels ranged from 14.0 to 28.0 µg/ml 3 hr after a dose of procainamide which is well above the 3-hr NAPA plasma levels of nonazotemic cardiac patients (range 1.9 to 6.3 µg/ml; p = 0.002) on larger doses of procainamide. There was almost no decline in NAPA plasma levels on interdialysis days. In one of the patients with renal failure NAPA was still present 15 days (13.8 µg/ml) and 38 days (0.9 µg/ml) after procainamide was stopped, indicating a half-life of several days. Measurement of procainamide plasma concentrations by the usual fluorometric or colorimetric methods does not detect NAPA. Since NAPA accumulates in patients with impaired renal function, the concentrations of both this active metabolite and procainamide should be determined in these patients if drug level monitoring is to be helpful.