• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of pharmacokinetics and biopharmaceutics >Do plasma concentrations obtained from early arterial blood sampling improve pharmacokinetic/pharmacodynamic modeling?
【24h】

Do plasma concentrations obtained from early arterial blood sampling improve pharmacokinetic/pharmacodynamic modeling?

机译：从早期动脉血采样中获得的血浆浓度是否改善了药代动力学/药效学模型？

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

In pharmacokinetic/pharmacodynamic (PK/PD) modeling the first blood sample is usually taken 1 to 2 min after drug administration (late sampling). Therefore, investigators have to extrapolate the plasma concentration to Time 0. Extrapolation, however, erroneously assumes instantaneous and complete mixing of drug in the central volume of distribution. We investigated whether plasma concentrations obtained from early arterial blood sampling would improve PK/PD modeling. In 14 pigs, one of five neuromuscular blocking agents (NMBAs) was administered into the right ventricle within 1 sec and arterial sampling was performed every 1.2 sec (1st min). The response of the tibialis muscle was measured mechanomyographically. The influence of inclusion of data from early arterial sampling on PK/PD modeling was determined. Furthermore, the concentrations in the effect compartment at 50% block (EC50) derived from modeling were compared to the measured concentration in plasma during a steady state 50% block. A very high peak in arterial plasma concentration was seen within 20 sec after administration of the NMBA. Extensive modeling revealed that plasma concentrations obtained from early arterial blood sampling improve PK/PD modeling. Independent of the type of modeling, the EC50 and KeO based on data sets that include early arterial blood sampling were, for all five NMBAs, significantly higher and lower respectively, than those based on data sets obtained from late sampling. Early arterial sampling shows that the mixing of the NMBA in the central volume of distribution is incomplete. A parametric PD (sigmoid Emax) model could not describe the time course of effect of the NMBAs adequately.
机译：在药代动力学/药效学（PK / PD）模型中，通常在给药后1-2分钟（首次采样）采集第一个血液样本。因此，研究人员必须将血浆浓度外推至时间0。但是，外推错误地认为药物在分配的中心体积中会立即完全混合。我们调查了从早期动脉血采样中获得的血浆浓度是否会改善PK / PD模型。在14头猪中，在1秒内将5种神经肌肉阻滞剂（NMBA）之一施用于右心室，每1.2秒（第1分钟）进行一次动脉采样。胫骨肌的反应是通过机械摄影法测量的。确定了从早期动脉采样中收集数据对PK / PD模型的影响。此外，将源自建模的50％阻滞（EC50）的效应隔室中的浓度与稳态50％阻滞期间血浆中的测量浓度进行了比较。服用NMBA后20秒内，动脉血浆浓度出现了非常高的峰值。广泛的建模显示，从早期动脉血采样中获得的血浆浓度可改善PK / PD建模。与建模类型无关，对于所有五个NMBA，基于包括早期动脉血采样在内的数据集的EC50和KeO分别明显高于基于晚期采样获得的数据集的EC50和KeO。早期的动脉采样显示，NMBA在中心分布容积中的混合不完全。参数PD（Sigmaxoid Emax）模型无法充分描述NMBA效应的时间过程。

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