Significance of acetylator phenotype in pharmacokinetics and adverse effects of procainamide.

The pharmacokinetics and development of antinuclear antibodies (ANAs) during procainamide (PA) therapy were studied in 35 patients with ventricular arrhythmias. Sixteen of the subjects were rapid and 19 were slow acetylators. Twenty-six of them (13 rapid and 13 slow acetylators) received PA therapy (2.4g sustained-release PA X HCl daily in three doses) for at least 16 weeks. On maintenance therapy, rapid acetylators had insignificantly lower serum PA concentrations and slightly higher N-acetylprocainamide (NAPA) concentrations than slow acetylators. The unchanged PA fraction (PA/PA + NAPA) in the rapid acetylators was somewhat lower than in the slow acetylators. Rapid acetylators excreted more NAPA in urine than did slow acetylators (p less than 0.05), whereas the difference in PA excretion was not significant. More than 80% of the given drug was excreted as PA and NAPA. Spontaneous or exercise-induced arrhythmias were recorded in 6 rapid and 8 slow acetylators. ANAs (titre at least 20) appeared in 6 rapid and 8 slow acetylators. The mean time until ANA development in rapid acetylators was only marginally longer than in slow acetylators. The results suggest that acetylation phenotyping is not of great significance in predicting the development of ANAs during PA therapy.