Capacity-limited elimination of procainamide in man

Procainamide (PA) pharmacokinetics were studied at steady state in 19 patients. The PA was given as 1.0 or 1.5 g eight hourly (L and H dose groups) and acetylator phenotype determined from sulphadimidine acetylation was classified as Slow or Fast (S or F). Thus, four groups were categorized, HF, LF, HS and LS with 7, 5, 3, and 4 patients in each respective group. Overall the mean steady state plasma concentration of PA (Cpss) expressed as a fraction of dose did not depend on dose or on acetylator status, but the HS group had significantly higher Cpss per gram dose (6.3 mug/ml) than LS (2.7 mug/ml) or the HF (2.3 mug/ml) groups. Clearance of PA be acetylation (C1A) was 23.8% of the total in fast acetylators and 16.5% in slow acetylators. C1A was not dose-dependent in the HF or LF groups (mean 177.9 ml/min and 168.4 ml/min) but was dose-dependent in the HS group (mean 74.6 ml/min) which differed significantly from the LS group (mean 113.4 ml/min).