DISPOSITION OF PROCAINAMIDE IN PATIENTS WITH CHRONIC CONGESTIVE-HEART-FAILURE RECEIVING MEDICAL THERAPY

Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are ba sed primarily on studies with unmatched control groups, suboptimal blo od sampling, and in patients not receiving angiotensin-converting enzy me (ACE) inhibitors. These agents increase renal blood flow, which the oretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CH F and in matched controls were compared, A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left v entricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respect ively, Patients with CHF and control subjects were demographically sim ilar, with the exception of concomitant medications, including ACE inh ibitors (8/9 versus 1/7, respectively). There were no significant diff erences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (C-max), area under the serum concentration- time curve (AUC(0-infinity)), total clearance, renal clearance, half-l ife (t(1/2)), or volume of distribution (Vd) of procainamide. Similarl y, there were no significant differences between patients with CHF and control subjects in the mean +/- SD C-max, AUC(0-infinity), renal cle arance, or t(1/2) of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.