An Open-Label Evaluation of the Effect of Coadministering Desvenlafaxine100 mg on the Pharmacokinetics of Aripiprazole in Healthy Subjects

Study background: The atypical antipsychotic aripiprazole is commonly coadministered with antidepressant drugs as an adjunctive treatment for depression. The goal of the current study was to assess the potential for multiple-dose treatment with the antidepressant desvenlafaxine (administered as desvenlafaxine succinate) to modify the pharmacokinetics of aripiprazole. Methods: Healthy subjects received aripiprazole 5 mg alone and coadministered with desvenlafaxine 100 mg at steady-state in an open-label, 2-period, sequential, inpatient/outpatient study. Blood samples collected prior to aripiprazole administration and for 14 days after each aripiprazole dose were analyzed for plasma aripiprazole and dehydro-aripiprazole concentrations. Aripiprazole area under the plasma concentration curve (AUC) over infinite time (AUCinf) and peak plasma concentration (Cmax) were determined for aripiprazole administered alone and coadministered with desvenlafaxine. Lack of an interaction was concluded if the 90% confidence intervals (CIs) for the ratio of adjusted geometric means for AUCinf and Cmax fell wholly within a prespecified acceptance range of 80% to 125%. Safety and tolerability were also assessed. Results: Aripiprazole AUCinf in the presence of steady state desvenlafaxine was 1584 ng•h/mL, compared with 1494 ng•h/mL for aripiprazole alone. The ratio of adjusted geometric mean (90% CI) was 106.0%, with CIs (101.4%, 110.8%) falling wholly within the prespecified acceptance range. The geometric mean Cmax of aripiprazole was 24.7 ng/mL for aripiprazole administered alone or with desvenlafaxine (ratio of adjusted geometric means [90% CI], 101.1% [92.9% to 109.9%]). Coadministration of desvenlafaxine with aripiprazole did not alter dehydroaripiprazole AUCinf, or Cmax (ratio of adjusted geometric means [90% CI], 102.9% [94.2%, 112.5%], and 106.3% [101.0%, 111.9%], respectively). Conclusions: Median plasma aripiprazole concentration-time profiles for single-dose administration of aripiprazole 5 mg alone and with steady-state desvenlafaxine 100 mg/d were nearly superimposable indicating that coadministration of multiple-dose desvenlafaxine 100 mg does not significantly alter aripiprazole pharmacokinetics.