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MK571 is a multidrug resistance protein-2 (ABCC2, Mrp2) inhibitor and has been widely used to demonstrate the role of Mrp2 in the cellular efflux of drugs, xenobiotics and their conjugates. Numerous reports have described modulation of Caco-2 cellular efflux and transport of flavonoids in the presence of MK571. Since flavonoids are efficiently conjugated by Caco-2/TC7 cells, we investigated the effects of MK571 on the efflux of flavonoid conjugates. The flavonol aglycones kaempferol, quercetin and galangin were efficiently taken up, conjugated and effluxed by Caco-2/TC7 cells. Apically-applied MK571 caused significant reductions in both the apical and basolateral efflux of flavonol conjugates from Caco-2/TC7 monolayers. MK571 did not significantly alter the apical:basolateral efflux ratio for flavonol conjugates, however, which is not consistent with MK571 specifically inhibiting only apical Mrp2. Since MK571 decreased the total amounts of conjugates formed, and increased cellular flavonol aglycone concentrations, we explored the possibility that MK571 also inhibits phase-2 conjugation of flavonols. MK571 dose-dependently inhibited the intracellular biosynthesis of all flavonol glucuronides and sulphates by Caco-2 cells. MK571 significantly inhibited phase-2 conjugation of kaempferol by cell-free extracts of Caco-2, and production of kaempferol-4′-O-glucuronide was competitively inhibited. These data show that MK571, in addition to inhibiting MRP2, is a potential inhibitor of enterocyte phase-2 conjugation.