Metabolism of Meso-2,3-Dimercaptosuccinic Acid in Lead-Poisoned Children and Normal Adults
Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy-metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination...
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| Veröffentlicht in: | Environmental health perspectives 1995-07, Vol.103 (7/8), p.734-739 |
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| creator | Asiedu, Patrick Moulton, Thomas Blum, Conrad B. Roldan, Erlinda Lolacono, Nancy J. Graziano, Joseph H. |
| description | Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy-metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional cross-over studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator. |
| doi_str_mv | 10.1289/ehp.95103734 |
| format | Article |
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While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional cross-over studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator.</description><identifier>ISSN: 0091-6765</identifier><identifier>EISSN: 1552-9924</identifier><identifier>DOI: 10.1289/ehp.95103734</identifier><identifier>PMID: 7588486</identifier><language>eng</language><publisher>United States: National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</publisher><subject>Adult ; Blood ; Child ; Child, Preschool ; Children ; Cholestyramine Resin - pharmacology ; Cross-Over Studies ; Dosage ; Eating ; Excretion ; Female ; Half lives ; Human resources ; Humans ; Infant ; Lead ; Lead - blood ; Lead - urine ; Lead poisoning ; Lead Poisoning - blood ; Lead Poisoning - metabolism ; Lead Poisoning - urine ; Liver Circulation ; Male ; Neomycin - pharmacology ; Pharmacokinetics ; Pilot Projects ; Succimer - administration & dosage ; Succimer - metabolism ; Urine</subject><ispartof>Environmental health perspectives, 1995-07, Vol.103 (7/8), p.734-739</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3854-e8cb942392d6c61613884d8c4fd0d70322bfca852eb9a8b8ca661a87c5ba749d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3432866$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3432866$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,864,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7588486$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asiedu, Patrick</creatorcontrib><creatorcontrib>Moulton, Thomas</creatorcontrib><creatorcontrib>Blum, Conrad B.</creatorcontrib><creatorcontrib>Roldan, Erlinda</creatorcontrib><creatorcontrib>Lolacono, Nancy J.</creatorcontrib><creatorcontrib>Graziano, Joseph H.</creatorcontrib><title>Metabolism of Meso-2,3-Dimercaptosuccinic Acid in Lead-Poisoned Children and Normal Adults</title><title>Environmental health perspectives</title><addtitle>Environ Health Perspect</addtitle><description>Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy-metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional cross-over studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator.</description><subject>Adult</subject><subject>Blood</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Cholestyramine Resin - pharmacology</subject><subject>Cross-Over Studies</subject><subject>Dosage</subject><subject>Eating</subject><subject>Excretion</subject><subject>Female</subject><subject>Half lives</subject><subject>Human resources</subject><subject>Humans</subject><subject>Infant</subject><subject>Lead</subject><subject>Lead - blood</subject><subject>Lead - urine</subject><subject>Lead poisoning</subject><subject>Lead Poisoning - blood</subject><subject>Lead Poisoning - metabolism</subject><subject>Lead Poisoning - urine</subject><subject>Liver Circulation</subject><subject>Male</subject><subject>Neomycin - pharmacology</subject><subject>Pharmacokinetics</subject><subject>Pilot Projects</subject><subject>Succimer - administration & dosage</subject><subject>Succimer - metabolism</subject><subject>Urine</subject><issn>0091-6765</issn><issn>1552-9924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkb1LxDAYh4Mo5_mxuQoZxMlqPpo0WYTj_IQ7ddDFJaRJ6kXa5kxawf_eyp2ik1OG38PDGx4ADjA6xUTIM7dYnkqGES1ovgHGmDGSSUnyTTBGSOKMF5xtg52UXhFCWHA-AqOCCZELPgbPc9fpMtQ-NTBUcO5SyMgJzS5846LRyy6k3hjfegMnxlvoWzhz2mYPwafQOgunC1_b6FqoWwvvQmx0DSe2r7u0B7YqXSe3v353wdPV5eP0JpvdX99OJ7PMUMHyzAlTypxQSSw3HHNMh9OsMHllkS0QJaSsjBaMuFJqUQqjOcdaFIaVusilpbvgfOVd9mXjrHFtF3WtltE3On6ooL36u7R-oV7Cu8KMECzFIDheC2J4613qVOOTcXWtWxf6pHCBiMCc_Q_mVFDMyQCerEATQ0rRVT_XYKS-oqkhmvqONuCHv3_wA68rDfvRan9NXYi_XYSiQg0GMmSln-CdnkE</recordid><startdate>199507</startdate><enddate>199507</enddate><creator>Asiedu, Patrick</creator><creator>Moulton, Thomas</creator><creator>Blum, Conrad B.</creator><creator>Roldan, Erlinda</creator><creator>Lolacono, Nancy J.</creator><creator>Graziano, Joseph H.</creator><general>National Institute of Environmental Health Sciences. 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While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional cross-over studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator.</abstract><cop>United States</cop><pub>National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare</pub><pmid>7588486</pmid><doi>10.1289/ehp.95103734</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central Open Access; JSTOR Archive Collection A-Z Listing; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult Blood Child Child, Preschool Children Cholestyramine Resin - pharmacology Cross-Over Studies Dosage Eating Excretion Female Half lives Human resources Humans Infant Lead Lead - blood Lead - urine Lead poisoning Lead Poisoning - blood Lead Poisoning - metabolism Lead Poisoning - urine Liver Circulation Male Neomycin - pharmacology Pharmacokinetics Pilot Projects Succimer - administration & dosage Succimer - metabolism Urine |
| title | Metabolism of Meso-2,3-Dimercaptosuccinic Acid in Lead-Poisoned Children and Normal Adults |
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