, Volume 49, Issue 4, pp 280-283

Sodium EDTA enhances intestinal absorption of two bisphosphonates

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Bisphosphonates are poorly absorbed when given orally and their absorption is subject to a large inter-and intraindividual variability. This poor absorbability is thought to result, at least in part, from formation of unabsorbable complexes with calcium. It was therefore investigated whether the calcium chelator EDTA could improve intestinal absorption of two bisphosphonates, 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), and dichloromethylenebisphosphonate (Cl2MBP). Absorption was assessed indirectly by measuring the suppression of hypercalcemia induced in thyroparathyroidectomized rats by a retinoid. The absorption of AHBuBP was in the range of 1–3%. EDTA increased absorption about tenfold at a AHBuBP dose of 0.6 mg P/kg and about twofold at lower doses, with the minimal effective dose of EDTA being 10 mg/kg. The absorption of Cl2MBP was also increased by EDTA, although to a smaller extent, the lowest effective dose being 100 mg/kg EDTA. Thus, EDTA can, in certain circumstances, increase the intestinal absorption of bisphosphonates. The mechanism might involve an increase in available bisphosphonate and a change in mucosal permeability. The amount of EDTA required is, however, too high for use clinically.