Influence of Aging on the Oxidative and Conjugative Metabolism of Propranolol.

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The influence of agihg an the hepatic metabolism of propranolol, i. e. conjuation, sidechain oxidaion and ring fxidation, was investigated in 32 inpatients aged 30 to 84 yr. Plasma propranolol concentaion and urinary main metabolites [propranolol glucuronide (PPLG), naphthoxylactic acid (NLA), and 4-hydroxypropranolol (4OHP) were measured after a single oral dose of 20mg propranolol. There were significant correlations between age and<BR>1) maximum propranolol concentration, 2) area unde the plasma concentration-time curve and 3) elimination half-life. Apparent oral clearance of propranolol was invesely correlated with age. Partial metabolic clearance (PMC) to 4OHP (ring oxidation) and PMC to NLA (side-chain oxidation) were significantly correlaed with age, while PMC to PPLG was not. In addition, the ratio of PMC to 4OHP to that of PMC to NLA was mot associated with age. These obserations suggest that there are age-related reductions in two oxidizing capacities, while there is no significant infuence of aging on the conugating capacity. The age-related reduction in oral clearance of propranolol may be Rainly caused by the decline in the capacity of two diffrent oxidation pathways.
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