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Do we need more iron-chelating drugs?
[...]even at the highest dose of ICL670 used (40 mg kg−1 day−1), the mean daily iron excretion achieved is 23 mg for a 50 kg man, which is higher than 15 mg achieved at the 20 mg kg−1 day−1 dose, but much lower than that achieved with deferiprone or deferox-amine in patients who have thalas-saemia,...
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Published in: | The Lancet (British edition) 2003-08, Vol.362 (9382), p.495-496 |
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description | [...]even at the highest dose of ICL670 used (40 mg kg−1 day−1), the mean daily iron excretion achieved is 23 mg for a 50 kg man, which is higher than 15 mg achieved at the 20 mg kg−1 day−1 dose, but much lower than that achieved with deferiprone or deferox-amine in patients who have thalas-saemia, with mean daily iron excretion of 27 mg and 42 mg at doses of deferiprone of 75 mg/kg and 100 mg/kg, respectively.2,3 The different pharmacokinetic profile of ICL670, including its slow rate of plasma clearance of half life of 12–16 h, limits the prospects of repeated administration and, consequently, its efficacy for iron removal.4 The ferrokinetic profile of ICL670, which results mainly in an increase of faecal iron excretion, and its slow clearance from blood suggests accumulation of the drug, its metabolites, and iron complexes in lipid-soluble compartments of serum proteins and tissues and the inability of iron complexes to be cleared through the kidneys. [...]properties increase the likelihood of toxic effects, similar to those of 8-hydroxyquinoline, which has similar lipophilicity to ICL670.5 Lipophilic chelators similar to ICL670, including 8-hydroxyquinoline, also cause an increase in the absorption of iron.4,5 A major drawback in understanding the ferrokinetic and pharmacodynamic characteristics of ICL670 is the absence of information about the isolation and characterisation of the metabolite(s) of ICL670, some of which may have iron-chelating properties. Another concern about ICL670 is the cost to patients—only if it is cheaper than deferoxamine and deferiprone will it benefit most of the patients with thalassaemia in developing countries.4 The introduction of new iron-chelating drugs may ultimately improve iron-chelation therapy for patients with thalassaemia and other disorders. |
doi_str_mv | 10.1016/S0140-6736(03)14085-8 |
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[...]properties increase the likelihood of toxic effects, similar to those of 8-hydroxyquinoline, which has similar lipophilicity to ICL670.5 Lipophilic chelators similar to ICL670, including 8-hydroxyquinoline, also cause an increase in the absorption of iron.4,5 A major drawback in understanding the ferrokinetic and pharmacodynamic characteristics of ICL670 is the absence of information about the isolation and characterisation of the metabolite(s) of ICL670, some of which may have iron-chelating properties. Another concern about ICL670 is the cost to patients—only if it is cheaper than deferoxamine and deferiprone will it benefit most of the patients with thalassaemia in developing countries.4 The introduction of new iron-chelating drugs may ultimately improve iron-chelation therapy for patients with thalassaemia and other disorders.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(03)14085-8</identifier><identifier>PMID: 12927446</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Benzoates - pharmacokinetics ; Benzoates - therapeutic use ; Chelation ; Deferoxamine - pharmacokinetics ; Deferoxamine - therapeutic use ; Developing countries ; Drug dosages ; Excretion ; Humans ; Iron ; Iron Chelating Agents - pharmacokinetics ; Iron Chelating Agents - therapeutic use ; Iron Overload - drug therapy ; Iron Overload - metabolism ; LDCs ; Metabolites ; Pharmacodynamics ; Pharmacokinetics ; Pyridones - pharmacokinetics ; Pyridones - therapeutic use ; Thalassemia - drug therapy ; Thalassemia - metabolism ; Triazoles - pharmacokinetics ; Triazoles - therapeutic use</subject><ispartof>The Lancet (British edition), 2003-08, Vol.362 (9382), p.495-496</ispartof><rights>2003 Elsevier Ltd</rights><rights>Copyright National Library of Medicine - MEDLINE Abstracts Aug 9 2003</rights><rights>Copyright Elsevier Limited Aug 9, 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-6edbd2b27cc5c3f6cc20b6ce18614308604bb2d339e9fb3ace5d907123f213203</citedby><cites>FETCH-LOGICAL-c463t-6edbd2b27cc5c3f6cc20b6ce18614308604bb2d339e9fb3ace5d907123f213203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12927446$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kontoghiorghes, George J</creatorcontrib><title>Do we need more iron-chelating drugs?</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>[...]even at the highest dose of ICL670 used (40 mg kg−1 day−1), the mean daily iron excretion achieved is 23 mg for a 50 kg man, which is higher than 15 mg achieved at the 20 mg kg−1 day−1 dose, but much lower than that achieved with deferiprone or deferox-amine in patients who have thalas-saemia, with mean daily iron excretion of 27 mg and 42 mg at doses of deferiprone of 75 mg/kg and 100 mg/kg, respectively.2,3 The different pharmacokinetic profile of ICL670, including its slow rate of plasma clearance of half life of 12–16 h, limits the prospects of repeated administration and, consequently, its efficacy for iron removal.4 The ferrokinetic profile of ICL670, which results mainly in an increase of faecal iron excretion, and its slow clearance from blood suggests accumulation of the drug, its metabolites, and iron complexes in lipid-soluble compartments of serum proteins and tissues and the inability of iron complexes to be cleared through the kidneys. [...]properties increase the likelihood of toxic effects, similar to those of 8-hydroxyquinoline, which has similar lipophilicity to ICL670.5 Lipophilic chelators similar to ICL670, including 8-hydroxyquinoline, also cause an increase in the absorption of iron.4,5 A major drawback in understanding the ferrokinetic and pharmacodynamic characteristics of ICL670 is the absence of information about the isolation and characterisation of the metabolite(s) of ICL670, some of which may have iron-chelating properties. Another concern about ICL670 is the cost to patients—only if it is cheaper than deferoxamine and deferiprone will it benefit most of the patients with thalassaemia in developing countries.4 The introduction of new iron-chelating drugs may ultimately improve iron-chelation therapy for patients with thalassaemia and other disorders.</description><subject>Benzoates - pharmacokinetics</subject><subject>Benzoates - therapeutic use</subject><subject>Chelation</subject><subject>Deferoxamine - pharmacokinetics</subject><subject>Deferoxamine - therapeutic use</subject><subject>Developing countries</subject><subject>Drug dosages</subject><subject>Excretion</subject><subject>Humans</subject><subject>Iron</subject><subject>Iron Chelating Agents - pharmacokinetics</subject><subject>Iron Chelating Agents - therapeutic use</subject><subject>Iron Overload - drug therapy</subject><subject>Iron Overload - metabolism</subject><subject>LDCs</subject><subject>Metabolites</subject><subject>Pharmacodynamics</subject><subject>Pharmacokinetics</subject><subject>Pyridones - pharmacokinetics</subject><subject>Pyridones - therapeutic use</subject><subject>Thalassemia - drug therapy</subject><subject>Thalassemia - metabolism</subject><subject>Triazoles - pharmacokinetics</subject><subject>Triazoles - therapeutic 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Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kontoghiorghes, George J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Do we need more iron-chelating drugs?</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2003-08-09</date><risdate>2003</risdate><volume>362</volume><issue>9382</issue><spage>495</spage><epage>496</epage><pages>495-496</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>[...]even at the highest dose of ICL670 used (40 mg kg−1 day−1), the mean daily iron excretion achieved is 23 mg for a 50 kg man, which is higher than 15 mg achieved at the 20 mg kg−1 day−1 dose, but much lower than that achieved with deferiprone or deferox-amine in patients who have thalas-saemia, with mean daily iron excretion of 27 mg and 42 mg at doses of deferiprone of 75 mg/kg and 100 mg/kg, respectively.2,3 The different pharmacokinetic profile of ICL670, including its slow rate of plasma clearance of half life of 12–16 h, limits the prospects of repeated administration and, consequently, its efficacy for iron removal.4 The ferrokinetic profile of ICL670, which results mainly in an increase of faecal iron excretion, and its slow clearance from blood suggests accumulation of the drug, its metabolites, and iron complexes in lipid-soluble compartments of serum proteins and tissues and the inability of iron complexes to be cleared through the kidneys. [...]properties increase the likelihood of toxic effects, similar to those of 8-hydroxyquinoline, which has similar lipophilicity to ICL670.5 Lipophilic chelators similar to ICL670, including 8-hydroxyquinoline, also cause an increase in the absorption of iron.4,5 A major drawback in understanding the ferrokinetic and pharmacodynamic characteristics of ICL670 is the absence of information about the isolation and characterisation of the metabolite(s) of ICL670, some of which may have iron-chelating properties. Another concern about ICL670 is the cost to patients—only if it is cheaper than deferoxamine and deferiprone will it benefit most of the patients with thalassaemia in developing countries.4 The introduction of new iron-chelating drugs may ultimately improve iron-chelation therapy for patients with thalassaemia and other disorders.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>12927446</pmid><doi>10.1016/S0140-6736(03)14085-8</doi><tpages>2</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Benzoates - pharmacokinetics Benzoates - therapeutic use Chelation Deferoxamine - pharmacokinetics Deferoxamine - therapeutic use Developing countries Drug dosages Excretion Humans Iron Iron Chelating Agents - pharmacokinetics Iron Chelating Agents - therapeutic use Iron Overload - drug therapy Iron Overload - metabolism LDCs Metabolites Pharmacodynamics Pharmacokinetics Pyridones - pharmacokinetics Pyridones - therapeutic use Thalassemia - drug therapy Thalassemia - metabolism Triazoles - pharmacokinetics Triazoles - therapeutic use |
title | Do we need more iron-chelating drugs? |
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