AGE AND PROPRANOLOL STEREOSELECTIVE DISPOSITION IN HUMANS

The apparent oral clearance of S(-)- and R(+)-propranolol as a function of age was evaluated in 53 healthy male volunteers (age range, 21 to 84 years) after a single 40 mg oral dose of the racemic mixture. No significant age-associated change in the total (bound plus unbound) and unbound S(-) and R(+) apparent oral clearance was observed (p > 0.05). Stereoselectivity in apparent oral clearance (both total and unbound) remained unaffected by advancing age (p > 0.05). The relationship between age and propranolol enantiomer plasma protein binding was also evaluated in 70 subjects, 53 of whom were from this study (age range, 21 to 89 years). Plasma free fractions for S(-)- and R(+)-propranolol were unchanged with increasing age (p > 0.05), even though the binding was stereoselective (plasma free fractions for R(+) > plasma free fractions for S(-); p < 0.05). The findings from this relatively large and extensive study indicate that age does not influence the steroselective disposition of propranolol.