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 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).
Syntex Research Centre, Heriot-Watt University Research Park, Riccarton, Edinburgh, UK.
W R
WR
Rush
D J
DJ
Hall
D J
DJ
Graham
I A
IA
Selby
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C044484:Imiloxan