Kinetics of the fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication
17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum...
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Veröffentlicht in: | European journal of clinical pharmacology 1986-01, Vol.30 (5), p.527-533 |
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description | 17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined during and after the infusion. The renal clearance of bound digoxin and therefore of the antibody was 13.6 ml/min. The median extrarenal clearance of the Fab fragments was 10.9 ml/min. The half-life of the serum concentrations starting at 12 h was 14.3 h, and the value was increased to 25.4 h when regression began at 24 h; the corresponding apparent distribution volumes were 25.9 and 541. These figures exceed the volume of the extracellular space and suggest intracellular penetration of the Fab fragments. The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning. The maximum serum concentrations of bound antibody were 30 mg/l after 3 h and 20 mg/l after 5 h. A loading dose of 160 mg followed by an infusion of 0.5 mg/min was sufficient to absorb digoxin re-diffusing into the serum during the first 8 h. In some cases free digoxin reappeared in the serum 8-12 h after beginning the treatment. This might be prevented by infusing a further ampoule at a rate of 0.1 mg/min or less. |
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The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined during and after the infusion. The renal clearance of bound digoxin and therefore of the antibody was 13.6 ml/min. The median extrarenal clearance of the Fab fragments was 10.9 ml/min. The half-life of the serum concentrations starting at 12 h was 14.3 h, and the value was increased to 25.4 h when regression began at 24 h; the corresponding apparent distribution volumes were 25.9 and 541. These figures exceed the volume of the extracellular space and suggest intracellular penetration of the Fab fragments. The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning. The maximum serum concentrations of bound antibody were 30 mg/l after 3 h and 20 mg/l after 5 h. A loading dose of 160 mg followed by an infusion of 0.5 mg/min was sufficient to absorb digoxin re-diffusing into the serum during the first 8 h. In some cases free digoxin reappeared in the serum 8-12 h after beginning the treatment. This might be prevented by infusing a further ampoule at a rate of 0.1 mg/min or less.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/BF00542410</identifier><identifier>PMID: 3758140</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Adolescent ; Adult ; Aged ; Animals ; Antigen-Antibody Reactions ; Biological and medical sciences ; Creatinine - blood ; Digoxin - immunology ; Digoxin - poisoning ; Digoxin - urine ; Drug intoxications. Doping ; Female ; Humans ; Immunoglobulin Fab Fragments - immunology ; Kinetics ; Male ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Protein Binding ; Sheep</subject><ispartof>European journal of clinical pharmacology, 1986-01, Vol.30 (5), p.527-533</ispartof><rights>1986 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c311t-7b4ee269a7b3990c9e739b99013b1c9d59e7deea98b2c2330a088d27df3dad8f3</citedby><cites>FETCH-LOGICAL-c311t-7b4ee269a7b3990c9e739b99013b1c9d59e7deea98b2c2330a088d27df3dad8f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8782157$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3758140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHAUMANN, W</creatorcontrib><creatorcontrib>KAUFMANN, B</creatorcontrib><creatorcontrib>NEUBERT, P</creatorcontrib><creatorcontrib>SMOLARZ, A</creatorcontrib><title>Kinetics of the fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><description>17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined during and after the infusion. The renal clearance of bound digoxin and therefore of the antibody was 13.6 ml/min. The median extrarenal clearance of the Fab fragments was 10.9 ml/min. The half-life of the serum concentrations starting at 12 h was 14.3 h, and the value was increased to 25.4 h when regression began at 24 h; the corresponding apparent distribution volumes were 25.9 and 541. These figures exceed the volume of the extracellular space and suggest intracellular penetration of the Fab fragments. The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning. The maximum serum concentrations of bound antibody were 30 mg/l after 3 h and 20 mg/l after 5 h. A loading dose of 160 mg followed by an infusion of 0.5 mg/min was sufficient to absorb digoxin re-diffusing into the serum during the first 8 h. In some cases free digoxin reappeared in the serum 8-12 h after beginning the treatment. This might be prevented by infusing a further ampoule at a rate of 0.1 mg/min or less.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Antigen-Antibody Reactions</subject><subject>Biological and medical sciences</subject><subject>Creatinine - blood</subject><subject>Digoxin - immunology</subject><subject>Digoxin - poisoning</subject><subject>Digoxin - urine</subject><subject>Drug intoxications. Doping</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin Fab Fragments - immunology</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Binding</subject><subject>Sheep</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1986</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkMtOwzAQRS0EKqWwYY-UBSukwEyc1PESKgqISmxgHfkxaY3apIpdHn-P-6AgWZqrOcezuIydI1wjgLi5GwMUeZYjHLA-5jxLEXI8ZH0AjulQCjhmJ96_A2AhgfdYj4uixBz6bPXsGgrO-KStkzCjpFY6qTs1XVATNkvrpu2XaxLVBKdb68jHaNdEt6sYfnl8SxXc5tunC7PE0wd19I-HOE1U2uaUHdVq7ulsNwfsbXz_OnpMJy8PT6PbSWo4YkiFzomyoVRCcynBSBJc6piQazTSFnFhiZQsdWYyzkFBWdpM2JpbZcuaD9jV9q7pWu87qqtl5xaq-64QqnV11V91Ub7YysuVXpDdq7uuIr_cceWNmseSGuP8XitFmWEh-A9toHdo</recordid><startdate>19860101</startdate><enddate>19860101</enddate><creator>SCHAUMANN, W</creator><creator>KAUFMANN, B</creator><creator>NEUBERT, P</creator><creator>SMOLARZ, A</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>19860101</creationdate><title>Kinetics of the fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication</title><author>SCHAUMANN, W ; KAUFMANN, B ; NEUBERT, P ; SMOLARZ, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c311t-7b4ee269a7b3990c9e739b99013b1c9d59e7deea98b2c2330a088d27df3dad8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Antigen-Antibody Reactions</topic><topic>Biological and medical sciences</topic><topic>Creatinine - blood</topic><topic>Digoxin - immunology</topic><topic>Digoxin - poisoning</topic><topic>Digoxin - urine</topic><topic>Drug intoxications. Doping</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin Fab Fragments - immunology</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Binding</topic><topic>Sheep</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHAUMANN, W</creatorcontrib><creatorcontrib>KAUFMANN, B</creatorcontrib><creatorcontrib>NEUBERT, P</creatorcontrib><creatorcontrib>SMOLARZ, A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHAUMANN, W</au><au>KAUFMANN, B</au><au>NEUBERT, P</au><au>SMOLARZ, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kinetics of the fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication</atitle><jtitle>European journal of clinical pharmacology</jtitle><addtitle>Eur J Clin Pharmacol</addtitle><date>1986-01-01</date><risdate>1986</risdate><volume>30</volume><issue>5</issue><spage>527</spage><epage>533</epage><pages>527-533</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined during and after the infusion. The renal clearance of bound digoxin and therefore of the antibody was 13.6 ml/min. The median extrarenal clearance of the Fab fragments was 10.9 ml/min. The half-life of the serum concentrations starting at 12 h was 14.3 h, and the value was increased to 25.4 h when regression began at 24 h; the corresponding apparent distribution volumes were 25.9 and 541. These figures exceed the volume of the extracellular space and suggest intracellular penetration of the Fab fragments. The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning. The maximum serum concentrations of bound antibody were 30 mg/l after 3 h and 20 mg/l after 5 h. A loading dose of 160 mg followed by an infusion of 0.5 mg/min was sufficient to absorb digoxin re-diffusing into the serum during the first 8 h. In some cases free digoxin reappeared in the serum 8-12 h after beginning the treatment. This might be prevented by infusing a further ampoule at a rate of 0.1 mg/min or less.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>3758140</pmid><doi>10.1007/BF00542410</doi><tpages>7</tpages></addata></record> |
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subjects | Adolescent Adult Aged Animals Antigen-Antibody Reactions Biological and medical sciences Creatinine - blood Digoxin - immunology Digoxin - poisoning Digoxin - urine Drug intoxications. Doping Female Humans Immunoglobulin Fab Fragments - immunology Kinetics Male Medical sciences Middle Aged Pharmacology. Drug treatments Protein Binding Sheep |
title | Kinetics of the fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication |
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