Summary
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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Brøsen, K., Klysner, R., Gram, L.F. et al. Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism. Eur J Clin Pharmacol 30, 679–684 (1986). https://doi.org/10.1007/BF00608215
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DOI: https://doi.org/10.1007/BF00608215