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. The substantial production of 2-hydroxy-desipramine, as reflected by the area under its concentration-time curve which was 51% to 94% of that for desipramine, indicates that accumulation will occur following multiple dosing. As 2-hydroxy-desipramine may possess antidepressant activity, future studies designed to assess the therapeutic effect of desipramine should account for the presence of its pharmacologically active metabolite.