Orally active alpha-ketohydroxypyridine iron chelators: studies in mice.

Several N-substituted 3-hydroxypyrid-2-one and N-substituted 2-methyl-3-hydroxypyrid-4-one chelators were screened for 59Fe removal using iron-overloaded mice labeled with 59Fe. The most effectice chelators were found to be the N-methyl, N-ethyl, and N-propyl derivatives of 2-methyl-3-hydroxypyrid-4-one. When the above three chelators were administered intragastrically or intraperitoneally (200 mg/kg) to mice, they caused equivalent 59Fe excretions to intraperitoneal desferrioxamine (200 mg/kg). These results increase the prospects for the use of the alpha-ketohydroxypyridine chelators in the treatment of iron overload.