Prazosin protein binding in health and disease.

Experiments have been performed using equilibrium dialysis to determine the binding of [C]-prazosin to albumin, to α-acid glycoprotein and to the plasma proteins of normal subjects and of patients with cirrhosis, chronic renal failure or chronic heart failure. The influence of propranolol on prazosin binding has been studied. In addition, red blood cell to plasma partitioning of prazosin has been quantified. The dissociation constant for prazosin binding to albumin was 3 × 10 M and to α-acid glycoprotein was 1.9 × 10 M. In fourteen normal subjects the free fraction of prazosin was 0.051 ± 0.007. In seven patients with cirrhosis free fraction of prazosin was 0.064 ± 0.017 ( < 0.05 compared to normal). In nine patients with chronic renal failure the free fraction was 0.077 ± 0.033 ( < 0.05) and in eight congestive heart failure patients the value was 0.064 ± 0.027 ( > 0.05). The range of prazosin free fraction was substantially greater in the patients than in normal subjects. In cirrhotic patients free fraction of prazosin correlated significantly ( = -0.92) with albumin concentration. Propranolol did not influence prazosin protein binding. In blood 20% of prazosin is associated with red cells. The considerably greater range of prazosin free fraction in the patients suggests that caution should be used when prescribing the drug for subjects with these conditions. Both albumin and the acute phase reactant α-acid glycoprotein bind prazosin