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Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat
Author(s) -
Barrand Margery A.,
Callingham Brian A.,
Dobbin Paul,
Hider Robert C.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12240.x
Subject(s) - chemistry , ferric , maltol , radiochemistry , tritium , metabolism , dissociation (chemistry) , chromatography , nuclear chemistry , inorganic chemistry , biochemistry , physics , nuclear physics
1 The fate and disposition of [ 59 Fe]‐ferric [ 3 H]‐maltol after intravenous administration were investigated in anaesthetized rats. Immediate dissociation of ferric iron from maltol took place in the circulation even with high doses of ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn within 1 min of injection and subjected to gel filtration, 59 Fe eluted with the high molecular weight proteins whilst the tritium was associated with low molecular weight material. 2 The rates of elimination of 59 Fe and of tritium from the plasma and their ultimate fate were very different. The half life for 59 Fe in the plasma was around 70 min and 59 Fe appeared mainly in the bone marrow and liver. There was an initial rapid exit of tritium from the plasma with a half life of around 12 min. This was followed either by a plateau or by a rise in tritium levels, involving entry of maltol metabolites into the circulation. These metabolites could be recovered in the urine. 3 Entry of 59 Fe and of tritium into the blood plasma after intraduodenal administration of [ 59 Fe]‐ferric [ 3 H]‐maltol was also very different. At low doses of ferric maltol (containing 100 μg elemental iron), the tritium appeared in the plasma in highest amounts within seconds and then decreased whilst there was a slow rise in 59 Fe levels. At higher doses of ferric maltol (containing 7 mg elemental iron), levels of 59 Fe in the plasma were highest at 5 min and then fell whereas tritium levels rose steadily. Mucosal processing of 59 Fe prevented further entry of iron at high dose into the circulation. 4 Initial rates of uptake of [ 3 H]‐maltol into isolated intestinal fragments were measured over a range of concentrations and revealed that maltol alone could diffuse freely into the tissues whereas maltol complexed to iron showed saturable uptake kinetics similar to those seen with the iron itself. 5 After intestinal uptake, 59 Fe and tritium were associated with different subcellular fractions, maltol itself being metabolized to the glucuronide conjugate within the intestinal mucosa. 6 It is concluded that dissociation of metal and ligand takes place before entry into the intestinal mucosa. Iron is then taken up on the endogenous carrier and processed in the normal way whilst maltol enters by diffusion, its rate of entry being limited by the degree of dissociation. It is subsequently metabolized by conjugation and eliminated rapidly from the body in the urine.