QUANTITATIVE DISPOSITION OF PROCAINAMIDE AND N-ACETYLPROCAINAMIDE IN RAT

  • 1 January 1978
    • journal article
    • research article
    • Vol. 204  (1) , 219-225
Abstract
The rat acetylator phenotype, the systemic availability of oral procainamide (PA) [an antiarrhythmic agent], the kinetic disposition of PA and its N-acetyl metabolite (NAPA), and the relationship between PA dose and steady-state blood PA and NAPA levels were investigated. The rat acetylator phenotype seems to be monomorphic in type. The systemic availability of PA was estimated to be 78%. The half-life (T1/2) of PA elimination was 55 min and that of NAPA was 51 min. PA clearance was 64 ml/kg per min and NAPA clearance 22.4 ml/kg per min. The apparent distribution volume for PA was 4.92 l/kg and for NAPA 1.64 l/kg. Acetylation accounted for 38% of PA disposition, urinary excretion 34% and other metabolism 28%. Urinary excretion of NAPA accounted for 72% of administered drug. Steady-state blood PA levels showed a linear increase with dose whereas NAPA did not. The latter observation suggests saturation of PA acetylation at higher PA doses.