Metabolism of amosulalol hydrochloride in man: Quantitative comparison with laboratory animals

Abstract

1. The metabolism of amosulalol hydrochloride, (±) -5-[1-hydroxy-2-[[2-(o-methoxyphenoxy) ethy1]amino]ethy1]-2-methylbenzenelphonamide hydrochloride, was studied in man and laboratory animals.

2. Humans excreted 30.1% of dose as unchanged drug, and the sulphate conjugate of a 5-hydroxy metabolite, (±)-5-[1-hydroxy-2-[[2-(5-hydroxy-2-methoxyphenoxy)ethy1]-amino]ethyl]-2-methylbenzenesulphonamide, was the major metabolite.

3. Amosulalol hydrochloride was extensively metabolized in animals with 10% or less excreted as unchanged drug. Hydroxylation of the 2-methyl group and O-demethylation of the o-methoxyphenoxy group were preferred in rats, and oxidative C-N cleavage yielding o-methoxyphenoxyacetic acid (M-5) preceded other reactions in dogs. Monkeys excreted almost equal amounts of the 5-hydroxy and 4-hydroxy metabolites as well as M-5.