title: N-acetylprocainamide kinetics during intravenous infusions and subsequent oral doses in patients with coronary artery disease and ventricular arrhythmias.
abstract: 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 X 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, less than 1 mg/L, were found at the end of the infusions.
authors.forename: T M
authors.initials: TM
authors.lastname: Ludden
authors.forename: M H
authors.initials: MH
authors.lastname: Crawford
authors.forename: G T
authors.initials: GT
authors.lastname: Kennedy
mesh_terms: D000120:Acecainide / Q000008:administration & dosage / Q000378:metabolism*; D000284:Administration, Oral; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D006207:Half-Life; D006352:Heart Ventricles; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011342:Procainamide / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D000120:Acecainide; D011342:Procainamide