Premium
Polymorphic acetylation of procainamide in man
Author(s) -
Reidenberg Marcus M.,
Drayer Dennis E.,
Levy Micha,
Warner Howard
Publication year - 1975
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1975176722
Subject(s) - procainamide , napa , chemistry , urine , pharmacology , medicine , biochemistry
N‐Acetylprocainamide (NAPA) and procainamide plasma and urine concentrations were determined by thin‐layer chromatography (TLC) densitometry in people of known acetylator phenotype (dapsone phenotyping) taking procainamide for more than 3 days. The plasma NAPA / procainamide ratio 3 hr after the last dose for fast acetylators (mean ± SD) is 1.8 ± 0.59 (N = 8) and for slow acetylators, 0.61 ± 0.09 (N = 6)(p < 0.001). The renal clearance of NAPA averaged 1.2 times the simultaneously measured endogenous creatinine clearance, whereas procainamide clearance was approximately double the creatinine clearance. There was no difference between slow and rapid acetylators in the renal clearance of either drug or the urine pH, indicating that the difference in plasma NAPA /procainamide ratios between these two groups is due to differences in their rates of acetylation. Therefore, procainamide is probably acetylated by the polymorphic N‐acetyltransferase in man. Reflecting the blood level differences, the NAPA/procainamide ratio in urine (collected 90 to 180 min after last dose) was found to be higher in rapid than in slow acetylators. The plasma protein binding of NAPA and of procainamide are similar. Since NAPA seems to have an antiarrhythmic potency similar to procainamide, NAP A probably contributes to the antiarrhythmic activity of procainamide therapy, especially in genetic rapid acetylators.