Plasma Concentration Monitoring of Hydroxylated Metabolites of Imipramine and Desipramine

Abstract

Steady-state serum concentrations of imipramine (IMI), its demethylated metabolite desipramine (DMI), and the active, hydroxylated metabolites, 2-hydroxy-imipramine (2-OH-IMI) and 2-hydroxy-desipramine (2-OH-DMI) were monitored in 126 psychiatric patients receiving IMI therapy. DMI and 2-OH-DMI concentrations were determined in a similar group of 61 DMI-treated patients. Although significant correlations exist between hydroxy metabolite and precursor concentrations, considerable variability was also found. Mean (± SD) ratios for the IMI patients were: 2-OH-IMI:IMI = 0.27 (± 0.19) and 2-OH-DMI:DMI = 0.56 (± 0.30). The ratio of DMI: IMI for males and 2-OH-DMI:DMI for females decreased with age (r = −0.42 and −0.32, respectively, p < 0.01). Variable metabolite concentrations and the uncertainty of their relative psychoactivity may contribute to the difficulties in relating antidepressant efficacy to serum concentrations of the administered IMI or DMI.