INFLUENCE OF AGING ON THE OXIDATIVE AND CONJUGATIVE METABOLISM OF PROPRANOLOL

The influence of aging on the hepatic metabolism of propranolol, i.e. conjugation, side-chain oxidation and ring oxidation, was investigated in 32 in-patients aged 30 to 84 yrs. Plasma propranolol concentration and main urinary metabolites [propranolol glucuronide (PPLG), naphtho xylactic acid (NLA), and 4-hydroxypropranolol (40HP)] were determined after a single oral dose of 20 mg propranolol. There were significant correlations between age and 1) maximum propranolol concentration, 2) area under the plasma concentration-time curve, and 3) elimination hal f-life. The apparent oral clearance of propranolol was inversely corre lated with age. Partial metabolic clearance (PMC) to 40HP (ring oxidat ion) and PMC to NLA (side-chain oxidation) were significantly correlat ed with age, while PMC to PPLG was not. These observations suggest tha t there are age-related reductions in two oxidizing capacities, while there is no significant influence of aging on the conjugating capacity . The age-related reduction in oral clearance of propranolol may be ma inly caused by the decline in the capacity of two different oxidation pathways.