Aripiprazole lauroxil: PBPK for Dosing Regimen and DDI Identification
Aripiprazole lauroxil (Aristada®) was approved by the FDA for treating schizophrenia in adults in October 2015 at monthly and 6-week dosing options. Although aripiprazole was not a new drug, Aristada was a new, long-acting injectable formulation to combat this challenging disease and improve adherence.
The sponsor needed to understand the impact of different dosing scenarios for this new injectable antipsychotic drug, including missing doses, since schizophrenia patients often struggle with medication adherence. This was accomplished by building a model using the Simcyp whole body physiologically-based pharmacokinetic (PBPK) Simulator for the evaluation of oral metabolism, combined with the Simulator’s MechDermA model for evaluation of the new intramuscular injection route of administration. PBPK modeling was able to show the drug uptake in the combination therapy (oral and injectable) for final drug labeling.
Schizophrenia is a chronic brain disorder, affecting approximately 1% of adults in the United States. It is associated with positive and negative symptoms including delusions, hallucinations, trouble concentrating, lack of motivation, flat affect, and impairments in cognitive and excutive function. Individuals with schizophrenia have trouble maintaining employment, but with effective treatment they can sometimes improve over time.
