Plasma concentration monitoring of hydroxylated metabolites of imipramine and desipramine.

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.

Excessive plasma concentration of tricyclic antidepressants resulting from usual doses: a report of six cases.

Six patients are described who achieved very high plasma concentrations of imipramine and desipramine during chronic therapy with usual doses. Side effects were minimal. Speculation as to apparent tolerance includes the presence of low metabolite concentrations.

Desipramine and 2-hydroxy-desipramine pharmacokinetics in normal volunteers.

Disposition characteristics of desipramine and its metabolite, 2-hydroxy-desipramine, were determined in four healthy male volunteers following an oral 50 mg dose of desipramine. Nonlinear least-squares regression of concentration-time data indicated that parent drug disposition could be described by a one-compartment open pharmacokinetic model for two subjects and by a two-compartment model for two subjects. The early appearance of 2-hydroxy-desipramine and its high peak concentrations indicates that desipramine probably undergoes pre-systemic elimination partly through formation of 2-hydroxy-desipramine.