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A variety of drugs that bind to iron have significant reductions in absorption when coadministered with iron compounds. Cimetidine has a structure that would suggest strong binding to iron ions. In vitro experiments were performed to examine a variety of characteristics of the binding of iron to cimetidine. Further studies were conducted to determine the effect of concurrent administration of ferrous sulfate on cimetidine absorption in an in vivo isolated perfused rat jejunal model of drug absorption. The dose of cimetidine was chosen to represent a human dose of 300 mg, while the ferrous sulfate doses were chosen to represent 150- and 300-mg doses. The higher ferrous sulfate dose completely inhibited cimetidine absorption (P < 0.01), while the lower dose of ferrous sulfate caused a 63% reduction in cimetidine absorption (P < 0.05). In vitro iron in its ferrous from rapidly oxidizes to the ferric form. The ferric form of iron binds to cimetidine and may be the cause of the decreased cimetidine absorption. Care should be taken in prescribing iron supplements with cimetidine.
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