Effect of aging on atenolol pharmacokinetics and pharmacodynamics

A study was conducted to characterize and compare the pharmacodynamics and pharmacokinetics of atenolol in young and elderly men. Six young (mean +/- SD, 25.0 +/- 3.0 years) and six elderly (63.0 +/- 3.2 years) healthy men took atenolol 100 mg orally once daily for 6 days. Heart rate response to submaximal exercise was measured at selected times for 48 hours, and plasma and urine samples were collected over the same time interval. The Sigmoid Emax model was fit to percent reductions in exercise heart rate and atenolol plasma concentrations. The younger men had significantly lower values for area under the steady-state plasma concentration-time curve and higher values for systemic clearance/F and renal clearance. EC50 values showed a trend toward greater sensitivity to the negative chronotropic effects of atenolol among the elderly men. Model-derived percent reductions in heart rate were greater at all concentrations among the elderly men. These data suggest that group differences in atenolol pharmacokinetics were likely a result of age-related decline in renal function, and that the elderly subjects were at least as sensitive as, and maybe even more sensitive than, the younger subjects to the negative chronotropic effects of atenolol.