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 a₂-adrenoceptor antagonist, was studied in four male volunteers given a 500 mg oral dose containing 0.48 MBq of the ¹⁴C-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).