Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism
Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine...
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Veröffentlicht in: | European journal of clinical pharmacology 1986-01, Vol.30 (6), p.679-684 |
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description | Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine 212 nmol/l; 2-OH-imipramine/imipramine 0.25; 2-OH-desipramine/desipramine 0.57. The corresponding values in two poor metabolizers were: imipramine 455 and 302 nmol/l; desipramine 1148 and 1721 nmol/l; 2-OH-imipramine/imipramine 0.06 and 0.05; 2-OH-desipramine/desipramine: 0.09 and 0.04 respectively. The metabolic ratios (MR) sparteine/dehydrosparteine and debrisoquine/4-OH-debrisoquine (% of dose in 12-h urine samples) correlated poorly with the imipramine steady-state concentrations during administration of 100 mg per day, but quite well with the desipramine steady-state concentrations. Significant negative correlations were found between sparteine and debrisoquine MR and the 2-OH-imipramine/imipramine and 2-OH-desipramine/desipramine ratios. In most patients the initial dose was changed to obtain concentrations in the therapeutic range, and concentrations for imipramine + desipramine of (mean +/- SD) 713 +/- 132 nmol/l were achieved in 33 patients. The therapeutic dose was 50 mg per day in one poor metabolizer and ranged from 50-400 mg per day in 32 extensive metabolizers. There was a weak negative correlation between sparteine MR and daily dose. Treatment with imipramine inhibited metabolism of both sparteine and debrisoquine (MR values about doubled), but did not affect the interpatient correlations. |
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F ; OTTON, S. V ; BECH, P ; BERTILSSON, L</creator><creatorcontrib>BRØSEN, K ; KLYSNER, R ; GRAM, L. F ; OTTON, S. V ; BECH, P ; BERTILSSON, L</creatorcontrib><description>Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine 212 nmol/l; 2-OH-imipramine/imipramine 0.25; 2-OH-desipramine/desipramine 0.57. The corresponding values in two poor metabolizers were: imipramine 455 and 302 nmol/l; desipramine 1148 and 1721 nmol/l; 2-OH-imipramine/imipramine 0.06 and 0.05; 2-OH-desipramine/desipramine: 0.09 and 0.04 respectively. The metabolic ratios (MR) sparteine/dehydrosparteine and debrisoquine/4-OH-debrisoquine (% of dose in 12-h urine samples) correlated poorly with the imipramine steady-state concentrations during administration of 100 mg per day, but quite well with the desipramine steady-state concentrations. Significant negative correlations were found between sparteine and debrisoquine MR and the 2-OH-imipramine/imipramine and 2-OH-desipramine/desipramine ratios. In most patients the initial dose was changed to obtain concentrations in the therapeutic range, and concentrations for imipramine + desipramine of (mean +/- SD) 713 +/- 132 nmol/l were achieved in 33 patients. The therapeutic dose was 50 mg per day in one poor metabolizer and ranged from 50-400 mg per day in 32 extensive metabolizers. There was a weak negative correlation between sparteine MR and daily dose. Treatment with imipramine inhibited metabolism of both sparteine and debrisoquine (MR values about doubled), but did not affect the interpatient correlations.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/bf00608215</identifier><identifier>PMID: 3533565</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Clinical Trials as Topic ; Debrisoquin - metabolism ; Depression - drug therapy ; Desipramine - analogs & derivatives ; Desipramine - metabolism ; Female ; Humans ; Hydroxylation ; Imipramine - analogs & derivatives ; Imipramine - metabolism ; Imipramine - therapeutic use ; Isoquinolines - metabolism ; Kinetics ; Male ; Medical sciences ; Middle Aged ; Neuropharmacology ; Pharmacology. Drug treatments ; Phenotype ; Polymorphism, Genetic ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. 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F</creatorcontrib><creatorcontrib>OTTON, S. V</creatorcontrib><creatorcontrib>BECH, P</creatorcontrib><creatorcontrib>BERTILSSON, L</creatorcontrib><title>Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><description>Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine 212 nmol/l; 2-OH-imipramine/imipramine 0.25; 2-OH-desipramine/desipramine 0.57. The corresponding values in two poor metabolizers were: imipramine 455 and 302 nmol/l; desipramine 1148 and 1721 nmol/l; 2-OH-imipramine/imipramine 0.06 and 0.05; 2-OH-desipramine/desipramine: 0.09 and 0.04 respectively. The metabolic ratios (MR) sparteine/dehydrosparteine and debrisoquine/4-OH-debrisoquine (% of dose in 12-h urine samples) correlated poorly with the imipramine steady-state concentrations during administration of 100 mg per day, but quite well with the desipramine steady-state concentrations. Significant negative correlations were found between sparteine and debrisoquine MR and the 2-OH-imipramine/imipramine and 2-OH-desipramine/desipramine ratios. In most patients the initial dose was changed to obtain concentrations in the therapeutic range, and concentrations for imipramine + desipramine of (mean +/- SD) 713 +/- 132 nmol/l were achieved in 33 patients. The therapeutic dose was 50 mg per day in one poor metabolizer and ranged from 50-400 mg per day in 32 extensive metabolizers. There was a weak negative correlation between sparteine MR and daily dose. Treatment with imipramine inhibited metabolism of both sparteine and debrisoquine (MR values about doubled), but did not affect the interpatient correlations.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Clinical Trials as Topic</subject><subject>Debrisoquin - metabolism</subject><subject>Depression - drug therapy</subject><subject>Desipramine - analogs & derivatives</subject><subject>Desipramine - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxylation</subject><subject>Imipramine - analogs & derivatives</subject><subject>Imipramine - metabolism</subject><subject>Imipramine - therapeutic use</subject><subject>Isoquinolines - metabolism</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Polymorphism, Genetic</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Sparteine - metabolism</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>eNo9kEFP3DAQhS3UCra0l96RfKh6qJQyE6_t5EgRtJWQegDO0cQZC1dJHGzvYf89ARZOc3jfexp9QnxF-IkA9rz3AAaaGvWR2OBW1RXCFj-IDYDCyrQWTsSnnP8DoG5BHYtjpZXSRm9EuS1Mw77KhQpLF2fHc0lUQpyzjF6GKSyJpjCzpHmQoWQ5caE-jqFwlmGWiccXXJYoywPLvFAqvBbOB-5TyPFx99xe4rifYloeQp4-i4-exsxfDvdU3F9f3V3-qW7-_f57eXFTOWVtqYwfhhpaPTQeBjLQ-i05QqNqUKAb7NEyWsOesSHvtsxcMxq2fdMbbJw6Fd9fd5e0fsG5dFPIjseRZo673FkLbYMIK_jjFXQp5pzYd0sKE6V9h9A9K-5-Xb8pXuGzw-qun3h4Rw9O1_zbIafsaPSJZhfyO2YbbW2r1ROo5IYR</recordid><startdate>19860101</startdate><enddate>19860101</enddate><creator>BRØSEN, K</creator><creator>KLYSNER, R</creator><creator>GRAM, L. F</creator><creator>OTTON, S. V</creator><creator>BECH, P</creator><creator>BERTILSSON, L</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><scope>7X8</scope></search><sort><creationdate>19860101</creationdate><title>Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism</title><author>BRØSEN, K ; KLYSNER, R ; GRAM, L. F ; OTTON, S. V ; BECH, P ; BERTILSSON, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-6fdd2095d8f0da609f4aca1632030581b17e176efe18afc4eee2e16e7b8b618c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1986</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Clinical Trials as Topic</topic><topic>Debrisoquin - metabolism</topic><topic>Depression - drug therapy</topic><topic>Desipramine - analogs & derivatives</topic><topic>Desipramine - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Hydroxylation</topic><topic>Imipramine - analogs & derivatives</topic><topic>Imipramine - metabolism</topic><topic>Imipramine - therapeutic use</topic><topic>Isoquinolines - metabolism</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenotype</topic><topic>Polymorphism, Genetic</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Sparteine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BRØSEN, K</creatorcontrib><creatorcontrib>KLYSNER, R</creatorcontrib><creatorcontrib>GRAM, L. F</creatorcontrib><creatorcontrib>OTTON, S. V</creatorcontrib><creatorcontrib>BECH, P</creatorcontrib><creatorcontrib>BERTILSSON, L</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><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BRØSEN, K</au><au>KLYSNER, R</au><au>GRAM, L. F</au><au>OTTON, S. V</au><au>BECH, P</au><au>BERTILSSON, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism</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>6</issue><spage>679</spage><epage>684</epage><pages>679-684</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Thirty-five imipramine treated patients were phenotyped with regard to polymorphic drug oxidation using sparteine and/or debrisoquine. During treatment with 100 mg imipramine per day the mean steady-state concentrations and ratios in 28 extensive metabolizers were: imipramine 169 nmol/l; desipramine 212 nmol/l; 2-OH-imipramine/imipramine 0.25; 2-OH-desipramine/desipramine 0.57. The corresponding values in two poor metabolizers were: imipramine 455 and 302 nmol/l; desipramine 1148 and 1721 nmol/l; 2-OH-imipramine/imipramine 0.06 and 0.05; 2-OH-desipramine/desipramine: 0.09 and 0.04 respectively. The metabolic ratios (MR) sparteine/dehydrosparteine and debrisoquine/4-OH-debrisoquine (% of dose in 12-h urine samples) correlated poorly with the imipramine steady-state concentrations during administration of 100 mg per day, but quite well with the desipramine steady-state concentrations. Significant negative correlations were found between sparteine and debrisoquine MR and the 2-OH-imipramine/imipramine and 2-OH-desipramine/desipramine ratios. In most patients the initial dose was changed to obtain concentrations in the therapeutic range, and concentrations for imipramine + desipramine of (mean +/- SD) 713 +/- 132 nmol/l were achieved in 33 patients. The therapeutic dose was 50 mg per day in one poor metabolizer and ranged from 50-400 mg per day in 32 extensive metabolizers. There was a weak negative correlation between sparteine MR and daily dose. Treatment with imipramine inhibited metabolism of both sparteine and debrisoquine (MR values about doubled), but did not affect the interpatient correlations.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>3533565</pmid><doi>10.1007/bf00608215</doi><tpages>6</tpages></addata></record> |
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subjects | Adult Aged Aged, 80 and over Biological and medical sciences Clinical Trials as Topic Debrisoquin - metabolism Depression - drug therapy Desipramine - analogs & derivatives Desipramine - metabolism Female Humans Hydroxylation Imipramine - analogs & derivatives Imipramine - metabolism Imipramine - therapeutic use Isoquinolines - metabolism Kinetics Male Medical sciences Middle Aged Neuropharmacology Pharmacology. Drug treatments Phenotype Polymorphism, Genetic Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Sparteine - metabolism |
title | Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism |
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