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
Hauptverfasser: BRØSEN, K, KLYSNER, R, GRAM, L. F, OTTON, S. V, BECH, P, BERTILSSON, L
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container_title European journal of clinical pharmacology
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creator BRØSEN, K
KLYSNER, R
GRAM, L. F
OTTON, S. V
BECH, P
BERTILSSON, L
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.
doi_str_mv 10.1007/bf00608215
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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. 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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 &amp; derivatives</subject><subject>Desipramine - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Hydroxylation</subject><subject>Imipramine - analogs &amp; 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. 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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. 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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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