N‐Acetylprocainamide Kinetics During Intravenous Infusions and Subsequent Oral Doses in Patients with Coronary Artery Disease and Ventricular Arrhythmias

The kinetics of N‐acetylprocainamide (NAPA) were studied in 5 patients (all men, mean age = 62) with coronary artery disease and ventricular arrhythmias during loading infusions of 0.22–0.45 mg/kg/min, prolonged (19–48 hrs) intravenous infusions 2.5–5.2 mg/min, and in 4 of the patients, during subsequent oral doses 1.5–3 g every 8 hrs. Serum, concentrations of NAPA were determined by high‐performance liquid chromatography. The individual concentration‐time profiles could, with one exception, be described by a two‐compartment, open, kinetic model with apparent first‐order elimination. The kinetic variables were: initial distribution volume (Vc) 0.20 ± 0.11 l/kg (mean ± SD); steady‐state distribution volume (Vss) 1.58 ± 0.55 l/kg; distributional clearance (Cle) 133 ± 23 ml/(kg·hr); absorption rate constant (Ka) 0.354 ± 0.173 hr⁻¹; and fraction of dose reaching systemic circulation (F) 1.00 ± 0.14. The data for one patient who had received increasing oral dosages of 1.5, 2, 2.5 and 3 g every 8 hours resulted in systematic underprediction of observed concentrations at the two highest oral dosing rates. This suggests the possibility of some degree of nonlinearity or time‐dependent change in the kinetic behavior of NAPA. Only low concentrations of procainamide, < 1 mg/L, were found at the end of the infusions. 1985 Pharmacotherapy Publications Inc.