Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazide acetylation phenotype

Abstract

To assess the extent of the acetylation of procainamide (PA) to N-acetylprocainamide (NAPA) in man, and its relation to isonicotinic acid hydrazide (INH) acetylation phenotype, the following study was done. Fourteen subjects received 500 mg of PA . HCI orally. INH acetylation phenotype was determined by the serum half-life of INH after 4 mg/kg of INH orally. Each urine voided for 96 hr after procainamide was saved and levels of procainamide and NAPA measured by gas-liquid chromatography. The 14 subjects eliminated 52 ± 4% ofthe dose as procainamide and 16 ± 2% ofthe dose as NAPA. Four fast INH acetylators eliminated 23 ± 3% ofthe dose as NAPA compared to 12 ± 1% by the slow acetylators (p < 0.05). The amount of unaltered procainamide excreted by thefast and slow INH acetylators was not significantly different, 50 ± 4% and 53 ± 4%, respectively. Ofthe total amount of drug recovered in the urine ofthefast and slow INH acetylators, NAPA accountedfor 32% and 19%, respectively (p < 0.01). There appears to be a positive correlation between the ability to acetylate INH and the ability to acetylate procainamide.