Influence of congestive heart failure on prazosin kinetics

The kinetics of oral prazosin was studied in 10 healthy normal subjects (NS) and in 9 patients with congestive heart failure (CHF). NS received a single 5-mg dose, and blood concentrations of prazosin (CB) were measured, using a specific HPLC assay, during an 8-hr period. CHF patients received a 2-mg dose after which CB was measured for 10 hr. These patients then received 2 to 5 mg prazosin every 8 hr for 48 hr. After the last dose of prazosin, CB was measured for 24 hr. After the initial dose, time to peak CB did not differ significantly between that of the NS (123 +/- 19 SEM min) and of patients with CHF (132 +/- 31.3 min). AUC/mg prazosin was greater (p less than 0.001) in patients with CHF (3,385 +/- 380 Ng x min/ml) than in NS (1,603 +/- 208 ng x min/ml). Elimination of prazosin from blood was slower in CHF patients (t1/2 = 374 +/- 33.4 min) than in NS (t1/2 = 144.5 +/- 4.3 min) (p less than 0.001). These data suggest that in patients with CHF the elimination of prazosin is substantially slower than in NS and therefore higher steady-state prazosin concentrations can be expected in CHF patients than in NS.