Dimethyl sulfoxide inhibits bioactivation of sulindac
Swanson, B.N.; Boppana, V.K.; Vlasses, P.H.; Rotmensch, H.H.; Ferguson, R.K.
Journal of Laboratory and Clinical Medicine 102(1): 95-101
1983
ISSN/ISBN: 0022-2143 PMID: 6854139 Document Number: 220423
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.