Development of a population pharmacokinetic model of olanzapine for Chinese health volunteers and patients with schizophrenia.
Development of a population pharmacokinetic model of olanzapine for Chinese health volunteers and patients with schizophrenia.
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DOI：
10.1136/bmjopen-2017-020070
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发表时间：
2018-08-17
期刊：
影响因子：
2.9
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Li A;Ji S;Yue W;Yan H;Dong F;Ruan C;Li W;Lu W;Zhang D;Wang C
奥氮平是一种非典型的抗精神病药物，通常用于治疗精神分裂症。然而，使用奥氮平仍有许多并发症，研究人员不断努力改进对定期治疗药物监测(TDM)数据的处理。本研究的目的是通过建立中国精神分裂症患者的群体药物动力学(PopPK)模型来优化奥氮平的个体化治疗。这项研究综合了健康志愿者在单次给药后的浓度数据，以及较少范围的TDM患者样本收集。利用非线性混合效应模型建立了PopPK模型。潜在的协变量，包括奥氮平制造商和患者的性别和年龄，在模型开发期间进行了评估。中国地区22名健康男性的616名血药浓度水平和中国12所医院男性和女性精神分裂症患者的458名血药浓度水平均纳入分析。浓度分布可用具有一级吸收和消除的两室模型来描述。不同剂型奥氮平的吸收速率(Ka)在2.85~5.39 h-1之间。典型的吸收时间延迟为0.877 小时。体重对中央隔室的表观体积有相当大的影响，并呈幂函数关系。本研究建立了中国精神分裂症患者奥氮平的PopPK模型。在确定奥氮平的PK参数后，结果表明体重对VC/F表现出相当大的影响，受试者和处方的影响有待进一步研究。本研究建立的PopPK模型可能为奥氮平的个体化治疗提供一定的信息。CHICCTR-TRC-10000934；结果。
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. 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. 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. 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. ChiCTR-TRC-10000934; Results.
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影响因子：
6.1
作者：
Comets, Emmanuelle;Brendel, Karl;Mentre, France
通讯作者：
Mentre, France
DOI：
10.1007/bf01060053
发表时间：
1980-01-01
期刊：
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS
影响因子：
--
作者：
SHEINER, LB;BEAL, SL
通讯作者：
BEAL, SL
影响因子：
3.2
作者：
Xue HB;Liu L;Zhang H;Montgomery W;Treuer T
通讯作者：
Treuer T
DOI：
10.2165/11532580-000000000-00000
发表时间：
2010-06-01
期刊：
Paediatric drugs
影响因子：
--
作者：
Lobo, Evelyn D;Robertson-Plouch, Carol;Bergstrom, Richard F
通讯作者：
Bergstrom, Richard F
影响因子：
4.6
作者：
Xiang, Yu-Tao;Kreyenbuhl, Julie;Shinfuku, Naotaka
通讯作者：
Shinfuku, Naotaka