Study of the metabolic pathways of alprenolol in man and the dog using stable isotopes

The metabolic pathways of alprenolol have been investigated in man and the dog, using an ion doublet technique of deuterium labelling combined with gas chromatography mass spectrometry. The drug is eliminated mainly by aromatic hydroxylation and glucuronidation. Specific analytical methods are applied to demonstrate that allylic oxidation and oxidative deamination are quantitatively of minor importance. The mechanism for oxidative deamination via an intermediary aldehyde could be elucidated by using the deuterium labelled compound. A method for characterization of 4-hydroxy-alprenolol glucuronides based on formation of stable derivatives and the following enzymatic hydrolysis is described. This approach has a general applicability to hydroxylated metabolites from compounds with an aminopropanol structure common for beta-adrenoceptor antagonists, for example. The metabolic routes for alprenolol in man and the dog are almost identical and in man more than 95% of a given dose can be accounted for.