NDLI: Population pharmacokinetic-pharmacodynamic (PopPK/PD) modeling of risperidone and its active metabolite in Chinese schizophrenia patients.

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Population pharmacokinetic-pharmacodynamic (PopPK/PD) modeling of risperidone and its active metabolite in Chinese schizophrenia patients.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ji, Shuangmin Shang, Dewei Wu, Kehua Li, Anning Li, Xiwei Deng, Chenhui Li, Liang Zhou, Tianyan Wang, Chuanyue Lu, Wei
Spatial Coverage	China
Abstract	PURPOSE: Risperidone is a second-generation antipsychotic agent commonly used in the treatment of ~ 31.1% of schizophrenia patients in China, it is the most commonly-prescribed antipsychotic agent. Despite the abundant use of risperidone, population pharmacokinetic-pharmacodynamic models of risperidone have not been performed in Chinese schizophrenia patients. The objective of this study was to develop a population pharmacokinetic-pharmacodynamic (PopPK/PD) model to describe the PK behavior and efficacy of risperidone and 9-hydroxy-risperidone (active metabolite) in Chinese patients. METHODS: Plasma concentration data (702 measurements from 131 patients) and positive and negative syndrome scale (PANSS) scores (258 observations from 56 patients) were analyzed using a nonlinear mixed-effects modeling (NONMEM) approach with first-order conditional estimation with interaction (FOCEI). The influence of potential covariates was evaluated. Model robustness was assessed using external validation, normalized prediction distribution error, nonparametric bootstrap, and visual predictive check approaches. RESULTS: Risperidone concentration data were well described by a one-compartmental model incorporating an additional compartment that refers to the concentration profiles of 9-hydroxy-risperidone. A complex absorption procedure was incorporated into the model to describe the metabolism of risperidone to 9-hydroxy-risperidone in the gastrointestinal (GI) tract. A binomial distribution in the estimated clearance (CL) of risperidone has been identified in our model. Decrease in PANSS score along with total AUC (AUCtotal) of risperidone and 9-hydroxy-risperidone was best characterized by an Emax model with 3 transit compartments describing the delay of drug effect. CONCLUSIONS: Considerable differences in PK behavior and drug effect of risperidone have been identified among Chinese extensive metabolizing (EM) and poor metabolizing (PM) patients. This PopPK/PD model may fulfill individualized treatment in clinical practice and may potentially be transferred to other antipsychotic therapies.
File Format	HTM / HTML
ISSN	09461965
Issue Number	5
Volume Number	54
Journal	Int. Journal of Clinical Pharmacology and Therapeutics
Language	English
Publisher	Dustri-Verlag
Publisher Date	2016-05-01
Publisher Place	Germany
Access Restriction	Subscribed
Subject Keyword	Discipline Pharmacology Antipsychotic Agents Pharmacokinetics Models, Biological Paliperidone Palmitate Risperidone Schizophrenia Drug Therapy Adult Administration & Dosage Blood Area Under Curve Asian Continental Ancestry Group Biotransformation China Epidemiology Female Humans Male Middle Aged Nonlinear Dynamics Phenotype Diagnosis Ethnology Schizophrenic Psychology Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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