Metabolism of procainamide in normal and cardiac subjects

N‐Acetylprocainamide (NAPA) has been well documented as a metabolite of pro cain amide (PA) in man. The objective of the present study was to separate and quantify PA and its metabolites in man. Ten subjects (5 normal and 5 patients with heart disease) were given 40 µCi of PA− 14 C orally, and samples of blood, urine, and expired air were collected for 72 hr. Each subject received 500 to 1,000 mg of PA (7 to 13 mg/kg). During the 72 hr after dosing, 73% to 91% of the dose was excreted in urine. During the first 24 hr, 31% to 56% of the dose [48 ± 2.2 (mean ± SEM)] was PA; 7% to 24% (15 ± 1.8) of the dose was NAPA; 6% to 10% (7 ± 0.5) of the dose was an unknown metabolite (R f = 0.0); and 2% to 4% (3 ± 0.2) of the dose was another unknown metabolite (R f = 0.3). No radioactivity was detected in expired air. Less than 0.2% of the dose was accounted for as either p‐aminobenzoic acid or as p‐acetamidobenzoic acid. The maximum concentration of PA in plasma for all 10 subjects was 5.6 ± 0.9 µg/ml, 4.2 ± 0.3 µg/ml for the normal subjects and 7.1 ± 1.4 µg/ml for the patients. The T½ for the elimination of PA was 2.9 ± 0.5 hr for the normals and 5.5 ± 0.9 hr for patients. The maximum concentration of NAPA in plasma for all subjects was 2.8 ± 0.6 µg/ml, 1.6 ± 0.3 µg/ml for normal subjects and 4.1 ± 0.8 µg/ml for patients. In 2 patients, concentrations of NAPA (4.0 and 5.6 µg/ml) were as high or higher than those of PA.