Author:
DeVane C. Lindsay,Jusko William J.
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.
Subject
Pharmacology (medical),General Pharmacology, Toxicology and Pharmaceutics
Cited by
19 articles.
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