beta blockade with pindolol: differential cardiac and renal effects despite similar plasma kinetics in normal and...

Cardiac and renal effects (measured as the reduction in exercise-induced tachycardia and PRA, respectively) and circulating drug concentrations after acute beta blockade with intravenous pindolol were compared between seven normal volunteers and six patients with terminal renal failure. Kinetic parameters were similar in both groups (total body clearance, 450 mg/min), indicating enhanced extrarenal elimination in patients. For any given drug concentration, however, the uremic patients responded to beta blockade with a greater decrease in pulse rate than did normal volunteers (P less than 0.001). Moreover, in the same group, the decrease of PRA was more marked (from 13.3 to 5.7 vs. 3.3 to 1.9 ng/ml/hr) and lasted longer (8 hours and more vs. 2 hours). Plasma aldosterone remained unchanged. These data reveal an increased dependency of both heart rate and renin release on beta adrenergic-mediated mechanisms in uremic man. They also show that kinetic findings in normal subjects cannot always be extrapolated to predict kinetic behavior in disease, and that similar kinetics do not imply similar effectiveness.