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.
That same PBPK model was leveraged to evaluate the impact of concomitant administration of strong CYP3A4 inhibitors and inducers and strong CYP2D6 inhibitors on the drug’s pharmacokinetics. Because patients that are CYP2D6 poor metabolizers have a reduced ability to eliminate CYP2D6 substrates, the sponsor also wanted to know if these patients would require dose adjustments. The effects of CYP3A and CYP2D6 modulators on different CYP2D6 phenotype groups (efficient, intermediate, and poor metabolizers) were provided via Simcyp PBPK modeling and simulation as in the label.