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The influence of aging on the stereoselective pharmacokinetics of propranolol in the rat
Author(s) -
Vermeulen An M.,
Belpaire Frans M.,
Moerman Emmanuel,
Smet Frits De,
Bogaert Marc G.
Publication year - 1992
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530040202
Subject(s) - propranolol , chemistry , enantiomer , pharmacokinetics , kinetics , stereoselectivity , free fraction , pharmacology , blood plasma , oral administration , endocrinology , plasma protein binding , stereochemistry , biochemistry , medicine , physics , quantum mechanics , catalysis
The influence of aging on the pharmacokinetics and the tissue distribution of (R)‐ and of (S)‐propranolol was studied in 3‐, 12‐, and 24‐month‐old rats. After both iv and oral administration of rac‐propranolol, the plasma concentrations were higher for the (R)‐ than for the (S)‐enantiomer. For the tissue concentrations, the reverse was true. The free 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 suggestion for a difference in tissue binding between the two enantiomers. With aging, the plasma and tissue concentrations of both enantiomers increase, probably due to a decrease in blood clearance. Tissue binding did not change much with aging. Notwithstanding the marked differences between the kinetics of the propranolol enantiomers, the changes which occur with aging affect both enantiomers to the same degree.