THE METABOLISM OF IMILOXAN HYDROCHLORIDE IN HEALTHY MALE-VOLUNTEERS

1. The metabolism of imiloxan hydrochloride [(+/-)-2-(1-ethyl-2-imidazoyl)methyl-1,4-benzodioxane hydrochloride], an alpha(2)-adrenoceptor antagonist, was studied in four male volunteers given a 500 mg oral dose containing 0.48 MBq of the C-14-labelled material. Compound-related radioactivity was rapidly excreted chiefly in the urine within 24 h of dosing. 2. Metabolites derived by initial oxidation on either or both the benzodioxane and imidazoyl moieties followed by glucuronic acid and sulphate conjugation, and an N-glucuronide of imiloxan were tentatively identified in urine. 3. The major urinary metabolites, comprising some 37-41% of the dose, appeared to be +/- 2-(1-ethyl-2-imidazoyl)methyl-1,4-benzodioxane-6/7-sulphonic acid (19% of dose), [+/- 2-(1-ethyl-2-imidazoyl)methyl-1,4-benzodioxane-6/7-ylium D-glucopyranoside]uronate (10-14% of dose), and a glucuronide conjugate of +/- 2-(1-ethyl-2-imidazoyl-4/5-hydroxy)methyl-1,4-benzodioxane (8% of dose).