Quinidine kinetics in congestive heart failure

The pharmacokinetics of quinidine was studied in cardiac patients with and without congestive heart failure. Following intravenous drug infusion, plasma and urine samples were collected at various times and analyzed for quinidine by a specific assay procedure. Although plasma quinidine concentrations varied over a wide range in both patient groups, the mean drug concentration at each time point was always higher in the congestive failure patients. In the 24‐hr postinfusion period, plasma drug disposition was biexponential with half‐life values for the fast and slow disposition processes (t_½α and t_½β) similar for each group. The respective values of t_½α and t_½β were 5.6 min and 6.8 hr in the congestive heart failure patients and 6.1 min and 6.2 hr in the control group. The volume of the central pool (V_c) and Vd_area were smaller in the congestive heart failure group (p < 0.05) with values of 0.44 ± 0.12 and 1.81 ± 0.49 L/kg, respectively, compared with those of the control group of 0.75 ± 0.31 and 2.67 ± 1.17 L/kg. Total body plasma drug clearance (Cl) was also lower in the heart failure patients (p < 0.05). The estimated Cl values were 3.16 ± 1.10 and 4.95 ± 1.36 ml/min/kg for the heart failure and control patients, respectively. Renal quinidine excretion accounted for 15% and 18% of the administered doses and corresponded to renal clearance values of 0.48 ± 0.15 and 0.95 ± 0.56 ml/min/kg in congestive heart failure and control patients, respectively. The results of this study indicate that the higher quinidine concentrations observed in congestive heart failure patients are due to a significantly smaller distribution volume for the drug.