Nonlinear desipramine kinetics: prevalence and importance.

Area of Science:

• Pharmacology
• Psychiatry
• Clinical Pharmacokinetics

Background:

• Tricyclic antidepressants (TCAs) plasma levels are used for dose adjustment in nonresponding patients.
• Current methods assume linear drug kinetics, but recent studies suggest nonlinear desipramine kinetics.
• Previous studies on desipramine nonlinearity were limited by small sample sizes.

Purpose of the Study:

• To investigate the kinetics of desipramine in a larger sample of depressed inpatients.
• To determine the prevalence and clinical significance of nonlinear desipramine pharmacokinetics.
• To assess the validity of linear kinetics assumptions for desipramine dose adjustments.

Main Methods:

• Plasma desipramine concentrations were measured in 42 depressed inpatients.
• Patients achieved steady-state conditions on a low initial dose and a subsequent higher dose.
• Concentrations were compared to predicted levels based on dose increases.

Main Results:

• Desipramine concentrations increased significantly more than predicted by dose increases in the overall sample.
• Substantial nonlinear changes (≥50% greater than expected increase) were observed in approximately one-third of the patients.
• For the majority of the sample, the observed increases in plasma concentration were not clinically significant.

Conclusions:

• While desipramine can exhibit nonlinear kinetics, this is not a universal phenomenon in depressed patients.
• Linear pharmacokinetics assumptions may be clinically acceptable for dose adjustments in a significant portion of depressed patients.
• Further research may be needed to identify predictors of nonlinear desipramine kinetics.