Active metabolites of imipramine and desipramine in man

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Abstract
Active hydroxy metabolites of imipramine (IMI) and desipramine (DMI) have been quantified in plasma and cerebrospinal fluid (CSF) from patients at steady‐state. In plasma of prepubescent boys and adults the concentration of unconjugated 2‐hydroxyimipramine is only 15% to 25% that of IMI; 2‐hydroxydesipramine (OH‐DMI) concentration, however, is usually 50% that of DMI and in some cases OH‐DMI is the predominant compound. In CSF from adult patients the ratio of concentrations OH‐DMI / DMI is higher than in plasma. Judging from the CSF / plasma ratio 12% of DMI exists in the free form at steady state, whereas 16% of OH‐DMI is free (P < 0.02). There is no evidence for saturation of hydroxylation within the therapeutic dose and concentration ranges investigated. On the basis of a steady‐state OH‐DMI/DMI ratio of Clinical Pharmacology and Therapeutics (1982) 31, 393–401; doi:10.1038/clpt.1982.50