2007 - København - Denmark

PAGE 2007: Applications- CNS
Marc-Antoine Fabre

Population pharmacokinetic analysis in children, adolescents and adults with schizophrenia or bipolar disorder

M.A. Fabre (2), E. Fuseau (2), A. Vermeulen (1), A. Thyssen (1).

(1) Johnson & Johnson Pharmaceutical Research & Development; (2) EMF Consulting, BP 2, 13545 Aix en Provence, France

Introduction: Risperidone is an effective and well-tolerated atypical antipsychotic. Oral risperidone is licensed for the treatment of schizophrenia and acute mania associated with Bipolar I disorder in adults. 

Objectives: To evaluate the pharmacokinetics (PK) of risperidone (RIS) and the active moiety (AM) in paediatric subjects with schizophrenia or bipolar disorder compared to adults using population PK analysis.Objectives: Text regarding objectives.

Methods: The population PK analysis of RIS and AM plasma concentrations was performed on rich and sparse data from three studies in paediatrics and six studies in adult subjects with either schizophrenia or bipolar disorder and included 304 children/adolescents (9-17 years) and 476 adults (18-71 years).  A two-compartmental population pharmacokinetic model was developed using nonlinear mixed effects modelling (NONMEM).  Age, sex, race, body weight, creatinine clearance (CRCL) and study were incorporated in the models to test as potential covariates. Since the dataset included children, adolescent and adult data, allometric scaling was used as a prior in the structural model.

Results/Conclusion: The AM and RIS concentrations were best described by a two-compartment disposition model with first order absorption and first order elimination.  CRCL, age and weight increased the clearance of the active moiety, which is unlikely to be of clinical relevance as simulated plasma concentrations were similar in children, adolescents and adults.

After including allometric scaling as a prior for clearances and volumes, none of the demographic or biochemical characteristics tested were found to have an effect on any of the PK parameters of risperidone. This suggests that the PK of risperidone was similar between children, adolescents and adults after accounting for body weight differences.

Reference: PAGE 16 (2007) Abstr 1116 [www.page-meeting.org/?abstract=1116]
Poster: Applications- CNS