HBED: The Continuing Development of a Potential Alternative to Deferoxamine for Iron-Chelating Therapy

To further examine the potential clinical usefulness of the hexadentate phenolic aminocarboxylate iron chelator N,N8-bis(2-hydroxybenzyl)ethylenediamine-N,N8-diacetic acid (HBED) for the chronic treatment of transfusional iron over-load, we performed a subchronic toxicity study of the HBED monosodium salt in rodents and have evaluated the iron excretion in primates induced by HBED. The HBED-induced iron excretion was determined for the monohydrochloride dihydrate that was first dissolved in a 0.1-mmol/L sodium phosphate buffer at pH 7.6 and administered to the primates either orally (PO) at a dose of 324 mmol/kg (149.3 mg/kg, n 5 5), subcutaneously (sc) at a dose of 81 mmol/kg (37.3 mg/kg, n 5 5), sc at 324 mmol/kg (n 5 5), and sc at 162 mmol/kg (74.7 mg/kg) for 2 consecutive days for a total dose of 324 mmol/kg (n 5 3). In addition, the monosodium salt of HBE