Plasma antipsychotic concentration and receptor occupancy, with special focus on risperidone long-acting injectable

Although effective plasma concentration ranges have been established for some antipsychotics, conventional and atypical, there is considerable inter-patient pharmacokinetic variation. Positron-emission tomography (PET) can be used to estimate D(2)-like receptor occupancy in the brain needed for an antipsychotic effect and the level above which extrapyramidal side effects (EPS) develop. For conventional antipsychotics, the window occupancy is approximately 70-80%. For the atypical antipsychotic risperidone, the antipsychotic effect starts at approximately 60% occupancy, with occupancy above 80% leading to EPS. The new formulation, risperidone long-acting injectable (RLAI), comprises risperidone in a biodegradable polymer. It is effective long-term at doses of 25 or 50 mg injected i.m. every 2 weeks. The constant and slow release of the long-acting formulation leads to less fluctuation in plasma levels and to a D(2)-like receptor occupancy which is below the threshold for EPS.