Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism

Ferrous sulfate and sodium sulfate reduce methyldopa absorption in humans. This current study was conducted to investigate some of the potential factors by which these compounds could reduce methyldopa absorption. A rat model developed to examine drug absorption was used. Solutions of 14C methyldopa alone and with ferrous sulfate or sodium sulfate were injected in vivo into closed duodenal segments. Ferrous sulfate reduced methyldopa absorption 52.9% (p less than 0.01), while sodium sulfate had no significant effect on methyldopa absorption. In vitro iron in its ferrous form rapidly oxidizes to the ferric form in the presence of methyldopa. The ferric form of iron binds strongly to methyldopa, presumably resulting in the decreased methyldopa absorption. Methyldopa was stable in vivo and in vitro in the presence of ferrous sulfate and sodium sulfate. These studies are consistent with ferrous sulfate reducing methyldopa absorption by the formation of ferric iron: methyldopa complexes.