जैवसमतुल्यता एवं जैवउपलब्धता जर्नल

अमूर्त

An Open-Label Evaluation of the Effect of Coadministering Desvenlafaxine 100 mg on the Pharmacokinetics of Aripiprazole in Healthy Subjects

Alice I Nichols, Shannon Lubaczewski, Yali Liang, Kyle Matschke, Gabriel Braley and Tanya Ramey

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 (AUC_inf) and peak plasma concentration (C_max) 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 AUC_inf and C_max fell wholly within a prespecified acceptance range of 80% to 125%. Safety and tolerability were also assessed.
Results: Aripiprazole AUC_inf 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 C_max 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 AUC_inf, or C_max (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.