Orally active α-ketohydroxy pyridine iron chelators intended for clinical use: in vivo studies in rabbits

Abstract

Summary Increased daily iron excretion from iron overloaded, ⁵⁹Fe lactoferrin labelled rabbits was observed following the intragastric administration of 1,2-dimethyl-3-hydroxy pyrid-4-one (L₁) or 1-ethyl-2-methyl-3-hydroxy pyrid-4-one (L₁-NE_t) at doses of 200 mg/kg. ⁵⁹Fe excretion induced by these drugs was predominantly faecal and was comparable to that caused by similar doses of subcutaneous or intramuscular desferrioxamine. The effectiveness of the two α-ketohydroxy pyridine chelators was confirmed by repeated administration, intragastrically or by subcutaneous or intramuscular injection, to the same or other rabbits. Examination of the urine during the administration of the chelators revealed their high specificity for iron but not for copper, zinc, calcium or magnesium.