Urinary desipramine hydroxylation index and steady-state plasma concentrations of imipramine and desipramine

An index of desipramine (DMI) hydroxylation, calculated as the ratio between the amounts of DMI and 2-hydroxydesipramine (2-OH-DMI) excreted in urine after 25 mg orally, was determined in 16 depressed patients. The index varied almost 100-fold between the patients and correlated significantly to the steady-state plasma concentrations of DMI (rs = 0.85; p less than 0.01) but not to the plasma levels of imipramine (IMI) when the patients were treated with 75 mg of IMI daily. Eleven of the 16 patients were subsequently treated with DMI and a significant relationship was again found between the plasma levels of DMI and the urinary DMI-hydroxylation index (rs = 0.87; p less than 0.01). The latter may be utilized in therapeutic drug monitoring to identify individuals with unusually rapid or slow hydroxylation of DMI.