title: Inhibition of sulindac metabolism by dimethyl sulfoxide in the rat.
abstract: Dimethyl sulfoxide (DMSO) suppresses conversion of the prodrug sulindac to its bioactive sulfide metabolite (SD) by competitively inhibiting sulfoxide reductase. During continuous iv infusions of sulindac (1 mg/kg X h), plasma concentrations of SD at steady-state equilibrium were 80% lower when DMSO was infused concomitantly at 0.34 ml/kg X h, whereas sulindac plasma concentrations were not significantly affected by DMSO. Dermal application and intragastric administration of DMSO also inhibited SD accumulation in plasma. DMSO was only a weak inhibitor of SD oxidation in vitro and did not affect the rate of SD elimination in vivo. In contrast, dimethyl sulfide, a metabolite of DMSO, was a potent inhibitor of SD oxidase in vitro. These data suggest that DMSO can inhibit bioactivation and, hence, the antiinflammatory effects of sulindac.
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004347:Drug Interactions; D066298:In Vitro Techniques; D007192:Indenes / Q000378:metabolism*; D007263:Infusions, Parenteral; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D013467:Sulindac / Q000097:blood / Q000378:metabolism*
chemical_list: D007192:Indenes; D013467:Sulindac; D004121:Dimethyl Sulfoxide