Stereoselective binding of propranolol in the elderly

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Geriatric Pharmacology
• Biopharmaceutical Sciences

Background:

• Age can influence drug pharmacokinetics, including protein binding.
• Propranolol exhibits stereoselective binding to serum proteins.
• Understanding age-related changes in drug binding is crucial for optimizing geriatric pharmacotherapy.

Purpose of the Study:

• To investigate the influence of age on the stereoselective serum protein binding of propranolol.
• To compare the free fraction of propranolol isomers in young versus elderly healthy male volunteers.

Main Methods:

• Serum samples were collected from young (mean age 23) and elderly (mean age 68) healthy male volunteers.
• Equilibrium dialysis was employed to measure the free fraction (fu) of tritium-labeled (+/-)- and (-)-propranolol.
• Serum alpha 1-acid glycoprotein (AAG) concentrations were quantified and correlated with propranolol binding.

Main Results:

• No significant differences in the free fraction of propranolol isomers were observed between young and elderly subjects.
• Serum alpha 1-acid glycoprotein (AAG) concentrations were comparable in both age groups (P > 0.05).
• AAG concentration variability explained most of the intersubject variability in propranolol isomer binding.

Conclusions:

• Age does not appear to significantly affect the stereoselective serum protein binding of propranolol.
• The binding characteristics of propranolol isomers remain consistent across young and elderly populations.
• AAG is a primary determinant of interindividual variability in propranolol binding, irrespective of age.