Lack of effect of ageing on the stereochemical disposition of propranolol

Abstract

The elderly are more resistant to the effects of propranolol than the young. To determine whether the decreased sensitivity in the elderly could be due to stereoselective alteration in propranolol metabolism, we investigated the effect of age on the oral clearance of (-)- and (+)-propranolol. Six young (aged 24-32, mean 27.3 +/- 1.3 years) and six elderly (65-80, mean 71.3 +/- 2.7 years) white male volunteers were given a single 80 mg oral dose of racemic propranolol. The mean peak plasma concentrations of both (+)- and (-)-propranolol were significantly higher (P less than 0.05) in the elderly (105.7 +/- 19.7 and 165.0 +/- 29.7 nmol l-1) compared with the young subjects (68.6 +/- 10.1 and 115.7 +/- 18.1 nmol l-1). The oral clearances of both (+)- and (-)-propranolol were significantly higher (P less than 0.05) in the young (6933 +/- 598 and 4554 +/- 372 ml min-1) than in the elderly (4548 +/- 712 and 2941 +/- 473 ml min-1). Age had no effect on the relative concentration of the two isomers. Thus, the ratio of (+)-propranolol to (-)-propranolol was 0.67 +/- 0.05 in the young compared with 0.65 +/- 0.02 in the elderly.