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Abstract
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 (0-24h) 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.