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Development of a population pharmacokinetic model of olanzapine for Chinese health volunteers and patients with schizophrenia.

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Development of a population pharmacokinetic model of olanzapine for Chinese health volunteers and patients with schizophrenia.

BMJ Open. 2018 Aug 17;8(8):e020070

Authors: Li A, Ji S, Yue W, Yan H, Dong F, Ruan C, Li W, Lu W, Zhang D, Wang C

Abstract
OBJECTIVE: Olanzapine is an atypical antipsychotic drug commonly used for the treatment of schizophrenia. However, there are still many complications associated with the use of olanzapine, and researchers continually strive to improve the handling of data from regular therapeutic drug monitoring (TDM). The objective of this study is to optimise the individualised treatment of olanzapine by establishing a population pharmacokinetics (PopPK) model in Chinese patients with schizophrenia.
METHODS: This study integrates an extensive collection of concentration data from healthy volunteers after a single dose and a less extensive collection of samples from patients undergoing TDM. A PopPK model was developed using non-linear mixed-effects modelling. Potential covariates, including the olanzapine manufacturer and patient gender and age, were assessed during model development. A total of 616 plasma concentration levels from 22 healthy male individuals in China and 458 concentration levels from 112 male and 122 female patients with schizophrenia undergoing TDM at 12 hospitals in China were included in the analysis. The concentration profile could be best described using a two-compartment model with first-order absorption and elimination.
RESULTS: The absorption rate (Ka) of olanzapine ranged from 2.85 h-1 to 5.39 h-1 for the different formulations. The typical absorption time delay was 0.877 hour. Body weight had a considerable effect on the apparent volume of the centre compartment and showed a power relationship.
CONCLUSIONS: A PopPK model of olanzapine in Chinese patients with schizophrenia was developed in this study. After determining the PK parameters of olanzapine, the results suggested that body weight exhibited a considerable impact effect on VC/F. The impact of subjects and formulations requires further study. The PopPK model established in this study is likely to provide some information for the individualised therapy of olanzapine.
TRIAL REGISTRATION NUMBER: ChiCTR-TRC-10000934; Results.

PMID: 30121590 [PubMed – in process]

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