Effects of amiodarone on kinetics of procainamide and its major metabolite disposition in rabbit

The effects of steady state amiodarone on the kinetics of procainamide (PA) and its major metabolite, acetylprocainamide (NAPA), disposition in rabbits were examined. When PA was given alone, the pharmacokinetic parameters alpha, beta, Kmo, K1m.V1.V-1m, were 0.20 +/- 0.04, 0.016 +/- 0.003, 0.027 +/- 0.01, and 0.043 +/- 0.02 min-1, respectively. When PA was given in combination with amiodarone, the corresponding values were 0.37 +/- 0.08, 0.0059 +/- 0.002, 0.0096 +/- 0.004, and 0.016 +/- 0.003 min-1, respectively. The results indicated that the disposition kinetics of both PA and NAPA were significantly changed by steady state amiodarone.