Hyperphosphatemia and IIo hyperparathyroidism are common and severe complications of chronic renal failure. Reduced dietary phosphorus has been shown to be an effective treatment in reducing serum phosphate and serum PTH. 2'-Phosphophloretin inhibited small intestine apical membrane Na+/phosphate cotransport and reduced serum phosphate in adult rats. 2'-PP and phosphoesters of phloretin were tested for inhibition of human small intestine brush border membrane alkaline phosphatase activity and for inhibition of Na+-dependent phosphate uptake. The IC50'S for inhibition of alkaline phosphatase suggested an order of inhibitory potency of 4-PP > phloretin > 4'-PP > 2'-PP. Inhibition of Na+-dependent phosphate uptake followed the sequence 2'-PP much greater than 4'-PP > 4-PP > phloretin. These results are consistent with 2'-PP being a specific inhibitor of human intestinal brush border membrane Na+/phosphate cotransport. (C) 2002 Elsevier Science (USA). All rights reserved.