INHIBITION OF N-ACETYLATION OF PROCAINAMIDE AND RENAL CLEARANCE OF N-ACETYLPROCAINAMIDE BY PARA-AMINOBENZOIC ACID IN HUMANS

Procainamide administration often results in excessively high serum N- acetylprocainamide (NAPA) concentrations and subtherapeutic serum proc ainamide concentrations, Inhibition of N-acetylation of procainamide m ay prevent accumulation of excessive NAPA while maintaining therapeuti c serum procainamide concentrations, The purpose of this randomized, t wo-way crossover study was to determine if para-aminobenzoic acid (PAB A) inhibits N-acetylation of procainamide in healthy volunteers. Eleve n (7 female, 4 male) fast acetylators of caffeine received, in random order, PABA 1.5 g orally every 6 hours for 5 days, with a single intra venous dose of procainamide 750 mg administered over 30 minutes on the third day, or intravenous procainamide alone. Blood samples were coll ected during a 48-hour period after initiation of the infusion. Urine was collected over a 72-hour period. Serum procainamide and NAPA conce ntrations were analyzed using fluorescence polarization immunoassay, U rine procainamide and NAPA concentrations were measured with high perf ormance liquid chromatography, PABA did not significantly influence to tal or renal procainamide clearance, elimination rate constant, AUC(0- infinity), amount of procainamide excreted unchanged in the urine, or volume of distribution. However, concomitant PABA administration with procainamide resulted in increases in NAPA AUC(0-infinity) and t(1/2) and reductions in NAPA Ke, procainamide acetylation (NAPA formation) c learance, and NAPA renal clearance. Although PABA inhibits metabolic c onversion of procainamide to NAPA, it also impairs the renal clearance of NAPA (but not procainamide) in healthy subjects. Therefore, PABA m ay not be useful for optimizing the safety or efficacy of procainamide in patients.