Dimethyl sulfoxide inhibits bioactivation of sulindac.
Sulindac, a nonsteroidal anti-inflammatory agent, is converted to a bioactive sulfide metabolite via reversible reduction of its sulfoxide moiety. To test whether DMSO can inhibit conversion of sulindac to its active form, eight healthy men received, in a randomized, crossover manner, 400 mg of sulindac, orally, either alone or 60 min after an oral dose of DMSO (30 ml, 70% solution). After the drug combination, mean plasma concentrations of the sulfide metabolite were significantly lower than in controls at 1.5, 2, 3, 4, and 8 hr after sulindac administration. The mean area under the plasma sulfide concentration-time curve for 0 to 12 hr was 30% (range 7% to 56%) lower after DMSO treatment. This study suggests that DMSO can inhibit metabolism of other sulfoxides in man and may antagonize the therapeutic efficacy of sulindac.
D000328:Adult; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005965:Glucuronates / Q000097:blood / Q000652:urine; D006801:Humans; D007192:Indenes / Q000378:metabolism*; D008297:Male; D013450:Sulfones / Q000097:blood / Q000652:urine; D013467:Sulindac / Q000097:blood / Q000378:metabolism* / Q000652:urine
D005965:Glucuronates; D007192:Indenes; D013450:Sulfones; D013467:Sulindac; D004121:Dimethyl Sulfoxide