Nonlinear desipramine kinetics: prevalence and importance.

Tricyclic antidepressant plasma levels have been used to guide dose adjustment in nonresponding patients, and recently 24-hour drug levels have been advocated for predicting therapeutic doses. Both methods of dose adjustment assume linear drug kinetics. Recent reports have suggested that desipramine kinetics are nonlinear, but the samples described were small, six subjects or fewer. In the current study, plasma desipramine concentrations were examined in 42 inpatients who were depressed who had achieved steady-state conditions with a low initial dose and subsequently with a higher dose. Desipramine concentrations increased significantly more than that predicted by the dose increase; however, only one third of the sample had substantial nonlinear changes (an increase in the concentration 50% greater than expected). In the remainder of the sample, disproportionate increases in plasma concentrations were not likely to be of clinical consequence.