• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Balanced designs in longitudinal population pharmacokinetic studies.
【24h】

Balanced designs in longitudinal population pharmacokinetic studies.

机译：纵向人群药代动力学研究中的平衡设计。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A simulation study was performed using a balanced design to determine the sample size required for accurate and precise estimation of a parameter at a given level of intersubject variability in a longitudinal population pharmacokinetic study. A two-compartment model parameterized in terms of clearance (Cl), volumes of the central (V1) and peripheral (V2) compartments, and intercompartmental clearance (Q) with multiple intravenous bolus inputs was assumed. Six samples were obtained from each subject using the informative profile (block) randomized design. Variability (in terms of coefficient of variation, CV) in model parameters was varied between 30% and 100%, and residual variability was fixed at 15%. Sample sizes ranging from 30 to 1,000 subjects were studied, and a hundred replicate data sets were generated and analyzed with NONMEM for each sample size at each CV. A sample size of 30 was required for accurate and precise estimation of structural model parameters when CV < or = 75%, except for Cl where it is adequate for CV < or = 100%. A sample size of 80 was required for intersubject variability estimation with CV < or = 60%. Robust estimates of variability in Cl were obtained with sample sizes of 30 (CV < or = 45%), 60 (CV 60-75%), and 100 (CV > or = 75%). Positively biased estimates of residual variability were obtained irrespective of sample size at > or = 60% CV. This indicates that estimates of residual variability obtained in study situations where CV > or = 60% should be interpreted with caution. In such situations model misspecification may not be the issue, because in this simulation study concentration-time profiles were generated and analyzed with the same model. Although these results should be interpreted within the context of the study, they provide a framework for addressing the issue of sample size in longitudinal population pharmacokinetic study with a balanced sampling design. The result of a population pharmacokinetic study can be anticipated by comparing the results of several simulations in which the various input factors have been varied.
机译：使用平衡设计进行模拟研究，以确定在纵向人群药代动力学研究中，在给定的受试者间变异性水平下，准确和精确估计参数所需的样本量。假设有一个两室模型，该模型根据间隙（Cl），中央室（V1）和外围室（V2）的容积以及具有多个静脉推注输入的室间间隙（Q）进行了参数设置。使用信息量分布（分组）随机设计从每个受试者中获取六个样本。模型参数的变异性（以变异系数CV表示）在30％和100％之间变化，而剩余变异性固定为15％。研究了30至1,000名受试者的样本量，并针对每个CV的每种样本量生成了一百个重复数据集并使用NONMEM进行了分析。当CV <或= 75％时，为准确和精确地估计结构模型参数，需要30个样本大小，但对于CV <或= 100％足够的Cl除外。 CV <或= 60％的受试者间变异性估计需要80个样本量。使用30（CV <或= 45％），60（CV 60-75％）和100（CV>或= 75％）的样本量获得Cl的可变性的可靠估计。无论样本大小在CV≥60％时，都获得了残留变异性的正偏差估计。这表明应谨慎解释在CV>或= 60％的研究情况下获得的剩余变异性估计值。在这种情况下，模型不合规格可能不是问题，因为在此模拟研究中，生成了浓度-时间曲线，并使用相同的模型进行了分析。尽管这些结果应在研究的背景下进行解释，但它们提供了一个框架，可解决采用平衡采样设计的纵向人群药代动力学研究中的样本量问题。可以通过比较几种模拟的结果来预测群体药代动力学研究的结果，在这些模拟中，各种输入因子已发生变化。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号