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 fo
r 48 hours, and plasma and urine samples were collected over the same
time interval. The Sigmoid E(max) 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 pl
asma concentration-time curve and higher values for systemic clearance
/F and renal clearance. EC(50) values showed a trend reward greater se
nsitivity to the negative chronotropic effects of atenolol among the e
lderly men. Model-derived percent reductions in heart rate were greate
r at all concentrations among the elderly men. These data suggest that
group differences in atenolol pharmacokinetics were likely a result o
f age-related decline in renal function, and that the elderly subjects
were at least as sensitive as, and maybe even more sensitive than, th
e younger subjects to the negative chronotropic effects of atenolol.