Pharmacokinetic-hemodynamic studies of disopyramide

The hemodynamic effects and pharmacokinetics of two doses of disopyramide (DP) given as a two-stage intravenous load and maintenance infusion were studied in anesthetized dogs. One group (n = 4) received 4 mg/kg for 30 min and 1 mg/kg/h for 30 min (low-dose group). The high-dose group (n = 4) received 8 mg/kg for 30 min and 4 mg/kg/h for 30 min. In the low-dose group, there was a fall in cardiac output which reached statistical significance at 300 min [from 3.4 +/- 0.4 (SD) to 2.7 +/- 0.7 L/min; p less than 0.05, analysis of variance (ANOVA)]. In the high-dose group, there also was a fall in cardiac output (from 4.6 +/- 1.4 to 3.0 +/- 0.4 L/min; p less than 0.01, ANOVA), and this was associated with a rise in total peripheral resistance (from 39 +/- 11 to 58 +/- 9 units; p less than 0.01). Peak total venous DP concentrations were 3.0 +/- 0.2 and 7.5 +/- 1.0 micrograms/ml for the low- and high-dose groups, respectively, and were achieved at the end of the load infusion. The free fraction of DP was not dependent on total venous DP concentration and approximated 0.66. Elimination half-life, clearance, and apparent volume of distribution were 3.91 +/- 0.53 h, 0.39 +/- 0.02 L/kg/h, and 2.22 +/- 0.32 L/kg, respectively, for the low-dose group and 3.67 +/- 0.91 h, 0.36 +/- 0.06 L/kg/h, and 1.84 +/- 0.29 L/kg, respectively, for the high-dose group. There were no significant differences between these measurements for low- versus high-dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)