Polymorphic acetylation of procainamide in man

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.

[1]  T. Gibson,et al.  Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazide acetylation phenotype , 1975, Clinical pharmacology and therapeutics.

[2]  F. Sjöqvist,et al.  Acetylation of procaine amide in man studied with a new gas chromatographic method. , 1974, British journal of clinical pharmacology.

[3]  D. Drayer,et al.  N-Acetylprocainamide: An Active Metabolite of Procainamide 1 , 1974, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[4]  D. Drayer,et al.  Hydralazine elimination in man , 1973, Clinical pharmacology and therapeutics.

[5]  E. Genton,et al.  Pharmacokinetics of procainamide. , 1972, Archives of internal medicine.

[6]  J. Peters,et al.  The diposition of the antileprotic drug dapsone (DDS) in Philippine subjects. , 1972, The American journal of tropical medicine and hygiene.

[7]  J. Bigger,et al.  Metabolism of procainamide in rhesus monkey and man , 1972, Clinical pharmacology and therapeutics.

[8]  J. Biggs,et al.  Binding of Dapsone and Monoacetyldapsone by Human Plasma Proteins 1 , 1971 .

[9]  J. Koch-weser,et al.  Procainamide dosage schedules, plasma concentrations, and clinical effects. , 1971, JAMA.

[10]  H. Perry,et al.  Relationship of acetyl transferase activity to antinuclear antibodies and toxic symptoms in hypertensive patients treated with hydralazine. , 1970, The Journal of laboratory and clinical medicine.

[11]  D. Alarcón-Segovia,et al.  Drug-induced lupus syndromes , 1969, British medical journal.

[12]  V. McKusick,et al.  Genetic Control of Isoniazid Metabolism in Man , 1960, British medical journal.

[13]  J. Cooper,et al.  The physiological disposition and cardiac effects of procaine amide. , 1951, The Journal of pharmacology and experimental therapeutics.

[14]  D. R. Gilligan.  BLOOD LEVELS OF SULFADIAZINE, SULFAMERAZINE AND SULFAMETHAZINE IN RELATION TO BINDING IN THE PLASMA , 1943 .

[15]  M. Friebová.  [Acetylation of drugs]. , 1974, Ceskoslovenska fysiologie.

[16]  M. Reidenberg.  Renal Function and Drug Action , 1971 .