Combined pharmacokinetic and pharmacodynamic model analysis for procainamide and its metabolite

The pharmacokinetic and pharmacodynamic profiles of procainamide (PA) and its major metabolite, acetylprocainamide (NAPA), were analyzed by extended combined pharmacokinetic and pharmacodynamic model in rabbits. The pharmacodynamic parameters Keo, S, Ce(50), Emax for PA were 0.023 +/- 0.005 min-1, 3.9 +/- 1.1, 3.6 +/- 0.9 micrograms.ml-1, 37 +/- 10 ms respectively and for NAPA were 0.061 +/- 0.017 min-1, 2.2 +/- 0.4, 6.2 +/- 1.7 micrograms.ml-1, 53.6 +/- 2.5 ms. Following PA iv to rabbit both PA and NAPA were involved in the QTc prolongation of the initial period, but the later action was mainly associated with NAPA. Differences of pharmacokinetic and pharmacodynamic parameters between PA and NAPA were found.