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报告的万古霉素在中国成年患者群体药代动力学模型的预测性能。

Predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients.

机构信息

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

出版信息

J Clin Pharm Ther. 2013 Dec;38(6):480-9. doi: 10.1111/jcpt.12092. Epub 2013 Sep 5.

Abstract

WHAT IS KNOWN AND OBJECTIVE

There are numerous studies on population pharmacokinetics of vancomycin in adult patients. However, there is no such research for Chinese adult patients. This study was conducted to evaluate the predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients and to identify some models appropriate for our population.

METHODS

A literature search was conducted in PubMed to obtain the population pharmacokinetic models of vancomycin published between December 2010 and September 2012. The models were assessed using concentration data collected from Chinese patients for external validation. Models with relatively poor predictability were excluded from further analysis. The performance of the remaining models was evaluated in patients with different levels of creatinine clearance, age, body weight and sex by Bayesian method. This method was also used to compare the predictive performance based on peak concentration and trough concentration and the predictability based on different number of observed concentrations.

RESULTS

One hundred and sixty-five blood concentrations from 72 Chinese adult patients were collected retrospectively to serve as the test data set. The evaluated models included all those reported in the seven publications reviewed by Marsot et al. and three other studies published after December 2010. Three models with poor performance on external validation were excluded from the next Bayesian analysis. The distribution of covariates in the model building data set had an important effect on prediction. The predictability based on peak/trough concentration was similar among the evaluated models, and no significant difference was found using our data set except for Roberts' model. As expected, an increased number of samples improved the performance of the Bayesian prediction.

WHAT IS NEW AND CONCLUSION

With our data set, the performance of the evaluated models varied. The characteristics of the patient population and distribution of covariates should be given more consideration when choosing a model to predict blood concentrations. The model developed by Purwonugroho et al. using a data set from patients similar to ours is appropriate for Bayesian dose predictions for vancomycin concentrations in our population of Chinese adult patients.

摘要

已知和目的

已有大量关于万古霉素在成年患者中的群体药代动力学的研究。然而,针对中国成年患者的此类研究却没有。本研究旨在评估已发表的万古霉素群体药代动力学模型在我国成年患者中的预测性能,并确定一些适合我国人群的模型。

方法

在 PubMed 中进行文献检索,以获取 2010 年 12 月至 2012 年 9 月间发表的万古霉素群体药代动力学模型。使用从中国患者中收集的浓度数据对模型进行外部验证。对预测能力较差的模型进行排除,不再进一步分析。通过贝叶斯法,对不同肌酐清除率、年龄、体重和性别患者的模型性能进行评估。该方法还用于比较基于峰浓度和谷浓度的预测性能,以及基于不同观测浓度数量的预测能力。

结果

回顾性收集了 72 例中国成年患者的 165 个血药浓度作为测试数据集。评估的模型包括 Marsot 等人综述的 7 篇文献中报道的所有模型,以及 2010 年 12 月后发表的另外 3 项研究。从下一步的贝叶斯分析中排除了 3 个外部验证性能较差的模型。模型构建数据集中协变量的分布对预测有重要影响。在评估的模型中,基于峰/谷浓度的预测性能相似,除 Roberts 模型外,使用我们的数据集中未发现显著差异。如预期的那样,样本数量的增加提高了贝叶斯预测的性能。

新内容和结论

使用我们的数据集,评估模型的性能有所不同。在选择用于预测血药浓度的模型时,应更多地考虑患者人群的特征和协变量的分布。Purwonugroho 等人使用与我们的患者数据相似的数据集开发的模型适合用于预测我国成年患者万古霉素血药浓度的贝叶斯剂量。

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