Some biochemical and pharmacological properties of an epoxide metabolite of alclofenac.

The properties of an epoxide metabolite of alclofenac have been investigated in a number of in vitro and in vivo tests. Alclofenac epoxide was shown to inhibit the activity of yeast alcohol dehydrogenase and form a conjugate with cysteine. The epoxide, but not alclofenac itself, showed mutagenic effects on strains of Salmonella typhimurium sensitive to alkylating agents, but had no effect on strains sensitive to intercalating agents. In addition the epoxide was active in a cell transformation assay using as a target Syrian hamster cells. No acute toxic reactions were observed in mice treated with alclofenac epoxide and the compound was devoid of analgesic and acute antiinflammatory activity. Alclofenac epoxide was found to be a sensitising agent in the guinea-pig when administered either by injection with complete Freud's adjuvant or topically as an ethanolic solution. It is postulated that the formation of the epoxide may explain some of the therapeutic and toxicological properties of alclofenac in man.