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  • Title: Enhanced biliary iron excretion with amphiphilic diethylenetriaminepentaacetic acid.
    Author: Adams PC, Lin E, Barber KR, Grant CW.
    Journal: Hepatology; 1991 Dec; 14(6):1230-4. PubMed ID: 1959873.
    Abstract:
    The elimination of toxic metal ions metabolically accumulated by patients remains a difficult clinical problem and a target of drug development. DTPA (diethylenetriaminepentaacetic acid) is a hydrophilic chelating agent with high affinity for divalent and trivalent metal ions including iron but with a limited ability to cross cell membranes for access to iron stores. In this study we have synthesized an amphiphilic form of this chelator-DTPA covalently linked to the phospholipid phosphatidylethanolamine (PE)--to produce a chelator that incorporates completely and stably into liposome membranes for efficient delivery to the liver and reticuloendothelial system. Biliary and urinary excretion of iron were studied in iron-loaded rats (n = 15) in association with a 2-hr intravenous infusion of sonicated liposomes of 1:1 amphiphilic phosphatidylethanolamine-DTPA/egg phosphatidylcholine (L-PE-DTPA) and compared with excretion obtained using equivalent amounts of water-soluble DTPA (alone or mixed with egg phosphatidylcholine liposomes [L-DTPA] as controls). For a 6-hr period, the administration of L-PE-DTPA resulted in approximately a 20-fold increase in biliary iron excretion (480 +/- 160 micrograms/6 hr, mean +/- S.D.) compared with that seen with DTPA (21.2 +/- 4.0 micrograms/6 hr) and L-DTPA (23.1 +/- 5.0 micrograms/6 hr) (p less than 0.05, analysis of variance). Urinary iron excretion was significantly decreased with L-PE-DTPA (41.5 +/- 38 micrograms/6 hr) compared with DTPA (154 +/- 110 micrograms/6 hr) and L-DTPA (86 +/- 17 micrograms/6 hr) (p less than 0.05). Combined biliary and urinary excretion of iron was three to four times greater with L-PE-DTPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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