A Pharmacokinetic Simulation-Based Comparison Of Varying Adherence Rates For Paliperidone ER And Risperidone In Patients With Schizophrenia

Authors: DeVane CL, Passarell JA, Fiedler-Kelly J, Ludwig E, Martinez L, Canuso CM
Conference: U.S. Psychiatric and Mental Health Congress
Keywords: compliance, dopamine, dosage regimen, Phase 1, Phase 3, psychiatry, psychotherapeutic agents, steady state, target bounds, two-compartment model, virtual
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Background

Medication adherence is important to successful management of • patients with schizophrenia and related psychotic disorders; patient nonadherence is documented in numerous studies (e.g., 30%-35% patient noncompliance).1,2 Drug formulation affects the pharmacokinetic (PK) profile and plays • an important role in maintaining therapeutic plasma concentrations.

Paliperidone extended-release (ER) and risperidone have similar • pharmacologic effects with regard to D2 receptor occupancy.3,4 Compared with risperidone, however, paliperidone ER formulation has a longer elimination half-life5 and less peak-to-trough fluctuations at steady state.

PK simulations using clinical study population data provide a novel • methodology to compare drug plasma concentrations following different adherence rates. PK simulations were performed to examine the impact of various • adherence rates during chronic therapy with paliperidone ER and risperidone.

U.S. Psychiatric and Mental Health Congress, Las Vegas, Nevada, November 2009

By C.L. DeVane; Julie Passarell; Jill Fiedler-Kelly; Elizabeth A. Ludwig; L. Martinez; C.M. Canuso