Acetylation of Procaine Amide in Man Studied With a New Gas Chromatographic Method

Abstract

A specific gas-chromatographic method was developed for determination of N-acetylprocaine amide in plasma and urine, using 4-amino-N-(2-piperidinoethyl)benzamide as an internal standard. The investigation was performed in 50 cardiac patients who had reached steady-state plasma concentrations of procaine amide. 2 The plasma concentrations of the acetylated metabolite varied between 1.0 and 15.0 mg/ml and were thus of the same order of magnitude as those of the parent drug. Especially high plasma levels of the metabolite were seen in patients with poor kidney function. 3 The urinary excretion of the metabolite varied markedly between individuals and ranged between 6 and 52% of the administered daily dose. There was a clear tendency towards higher rates of acetylation of procaine amide in patients with short plasma half-lives of isoniazid, i.e. the phenotype rapid acetylators. Because of coexisting therapy with other drugs and impaired renal function in some patients studies are required in healthy human volunteers to ascertain whether the acetylation of procaine amide and isoniazid are mediated by the same enzyme system.

Interindividual Variability in 5-Fluorouracil Metabolism and Procainamide N-Acetylation in Human Liver Cytosol

“…Gibson et al 14) reported 7 to 34% N-acetylprocainamide recovery in 24 h in normal volunteers after a single oral dose of procainamide, and Karlsson et al 15) reported 6 to 53% recovery in 24 h in patients who were being given procainamide chronically.…”

Metabolism of procainamide in normal and cardiac subjects

“…The suggestion has been made that the slow acetylators of PA may be at greater risk of developing druginduced side effects (such as the syndrome resembling systemic lupus erythematosus, SLE) as do the slow acetylators of the bimodally acetylated drugs hydralazine, 20 isoniazid, 17, 14,21 and phenelzine. sit has been reported that it may be possible to predict PA phenotype by determining the rate of acetylation of other drugs l2 , 17,22,23 or by measuring the plasma or urinary ratio of NAPA/PA in timed samplesY After our study was completed, one of our patients, R. H., who had been on PA (750 mg every 6 hr) for 1 yr, was readmitted to the hospital with an SLE-like syndrome, probably induced by PA. He complained of migratory arthralgias and arthritis and had a pericardial effusion, pericardial friction rub, fever, positive antinuclear antibody, and 3 positive LE cell preparations…”

Adverse reactions to procainamide.

“…One of the major recent advances in this area has been the discovery of the polymorphic nature of procainamide acetylation (Karlsson, Molin, Norlander & Sjoqvist, 1974;Reidenberg, Drayer, Levy & Warner, 1975) and its relation to toxicity, both shortterm cardiovascular effects (Campbell, Tilstone, Lawson, Hutton & Lawrie, 1976), and induction of lupus erythematosis (Karlsson et al, 1974;Davies, Beedie & Rawlins, 1975). Unfortunately, in the Campbell et al (1976) reported that procainamide interferes with the use of sulphadimidine as a marker for acetylator capacity.…”