Procainamide is almost completely absorbed after oral administration and peak plasma concentrations are generally reached within 1 to 2 hours. Upon intravenous administration there is a rapid initial distribution phase, which is completed after about 30 minutes. The pharmacokinetics can be described by a 2-compartment open model. The plasma half-life during the &bgr;-phase averdges 3 hours. The apparent volume of distribution is about 2L/kg body weight. At therapeutic plasma levels about 15% is bound to plasma proteins.Approximately 50% of administered procainamide is eliminated as unchanged drug via the kidneys. N-Acetylprocainamide is the main metabolite and is pharmacologically active, with a recovery in urine of about 15% (range 7 to 34% in healthy subjects). The acetylation of procainamide seems to be under the same monogenic control as that of isoniazid. At least 2 more metabolites have been found but are not yet identified. The renal clearance of procainamide ranges from 179 to 660ml/min. Glomerular filtration and active tubular secretion seem to be the most important mechanisms.In patients with low-output cardiac failure and/or renal impairment, the absorption, distribution and elimination of the drug may be significantly altered. Determination of plasma levels is of particular value in these cases and will contribute to more safe and effective therapy in the majority of patients. As N-acetylprocainamide seems to have pharmacological effects comparable with those of procainamide, both agents should be monitored simultaneously in order to optimise therapy.