Biotransformation of tolmesoxide in animals and man

1. The excretion and metabolism of tolmesoxide ((4,5-dimethoxy-2-methylphenyl)-methylsulphoxide) has been studied in rat, dog and man. In all species, absorption of oral doses of [14C]tolmesoxide was virtually complete and 78--99% of the 14C was excreted in the urine. 2. In bile-duct cannulated rats, excretion in bile and urine was 49% and 53% dose respectively. Metabolites of tolmesoxide in bile undergo enterohepatic circulation with final elimination by the kidneys. 3. Quantification and identification of metabolites in urine (0-24 h) were obtained by two-dimensional t.l.c. Tolmesoxide was extensively metabolized in all animal species. 4. The major routes of metabolism in rat, dog and man were oxidation to sulphones and O-demethylation followed by sulphate or glucuronide conjugation. Little or none of the urinary 14C was present as sulphide derivatives.