Original Article: PDF OnlyTenero David M.; Bottorff, Michael B.; Burlew, Brad S.; Williams, James B.; Lalonde, Richard L.Journal of Cardiovascular Pharmacology: November 1990 - p 702-707 Free Abstract Summary: The elderly are reported to be less sensitive to the β-blocking effects of propranolol. However, agerelated changes in the stereoselective pharmacokinetics or protein binding of propranolol enantiomers could have confounded the results of previous studies because only 1-propranolol contributes significantly to the β-blocking effects of the racemate. To avoid these confounding variables, we studied 10 young (mean 28 years) and 10 elderly (mean 64 years) subjects, and determined the cardiac P-receptor sensitivity in terms of unbound, active 1-propranolol. The doses of isoproterenol required to increase heart rate (HR) by 25 beats/min were determined before and during a continuous infusion of propranolol. The serum concentration of 1-propranolol was determined by enantioselective high-performance liquid chromatography (HPLC), and the unbound fraction was determined by equilibrium dialysis. The apparent in vivo receptor dissociation constant for unbound 1-propranolol increased from 0.066 ± 0.047 ng/ml in the young to 0.218 ± 0.264 ng/ml in the older group (p<0.05). The unbound fraction was decreased in the older subjects (0.141 ± 0.023 vs. 0.121 ± 0.025, p<0.05) because of an increase in α1-acid glycoprotein concentration (55 ± 11 mg/dl vs. 72 ± 19 mg/dl, p<0.05). Advancing age was associated with a decreased sensitivity to isoproterenol (r s=0.76, p<0.05) and to unbound 1-propranolol (rs=0.45, p<0.05). We conclude that the older subjects have (a) decreased sensitivity to the β-blocking effects of 1-propranolol and to the agonist effects of isoproterenol, and (b) a lower unbound fraction of 1-propranolol © Lippincott-Raven Publishers.