Active metabolites of imipramine and desipramine in man.
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 of 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 less than 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 less than 1/30 in plasma 5% of the population studied could be classified as deficient DMI hydroxylators. This in the same as the incidence of deficient debrisoquine hydroxylators reported in other populations.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001711:Biotransformation; D002648:Child; D003891:Desipramine / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000627:therapeutic use; D004311:Double-Blind Method; D004775:Enuresis / Q000188:drug therapy; D005260:Female; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
C033803:2-hydroxyimipramine; D007099:Imipramine; D003891:Desipramine; C028653:2-hydroxydesipramine