THE INFLUENCE OF AGING ON THE STEREOSELECTIVE PHARMACOKINETICS OF PROPRANOLOL IN THE RAT

The influence of aging on the pharmacokinetics and the tissue distribu tion of (R)- and of (S)-propranolol was studied in 3-, 12-, and 24-mon th-old rats. After both iv and oral administration of rac-propranolol, the plasma concentrations were higher for the (R)- than for the (S)-e nantiomer. For the tissue concentrations, the reverse was true. The fr ee fraction of (S)-propranolol in plasma was about 4 times larger than that of (R)-propranolol, and this is the main factor responsible for the differences in kinetics between the two enantiomers. There was a s uggestion for a difference in tissue binding between the two enantiome rs. With aging, the plasma and tissue concentrations of both enantiome rs increase, probably due to a decrease in blood clearance. Tissue bin ding did not change much with aging. Notwithstanding the marked differ ences between the kinetics of the propranolol enantiomers, the changes which occur with aging affect both enantiomers to the same degree.