Design of optimal two-sample bolus injection tests for measuring low plasma clearance rates
Design of optimal two-sample bolus injection tests for measuring low plasma clearance rates
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DOI：
10.1016/s0169-2607(98)00083-2
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发表时间：
1999-02-01
影响因子：
6.1
通讯作者：
Thomaseth, K
中科院分区：
文献类型：
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作者：
Thomaseth, K
大剂量注射技术被广泛用于评估物质的血浆清除率，它是基于多次浓度测量的多指数数据分析。如果公寓间混合发生的速度比消除的速度快得多，即血浆清除率低，这种方法可以简化为只有两个测量值的单指数描述。在这种情况下，初始瞬态必须忽略，因为如果混合仍然不完全，第一个测量时间瞬间会影响间隙估计的准确性。此外，测量噪声影响估计精度，可通过适当选择采样计划和注射试验剂量来优化估计精度。本研究的目的是设计双样品丸注射试验，以预先设定的精度和最少的注射试验物质量来测量低血浆清除率。本文提供了评价等离子体间隙是否足够低以允许等离子体消失曲线的单指数描述和选择第一次采样时间瞬间的方程。提出了确定最佳试验剂量和二次采样时间的封闭方程。结果导出了一个特定的异方差测量噪声描述，鲁棒性的问题，相对于患者间的可变性动力学参数被解决。1999爱思唯尔科学爱尔兰有限公司版权所有。
The bolus injection technique is widely used for assessing plasma clearance rates of substances and is based on multiexponential data analysis of multiple concentration measurements. This approach can be simplified to a monoexponential description with only two measurements if intercorapartmental mixing occurs at a much faster rate than elimination, i.e. with low plasma clearance rates. In this context initial transients must be ignored because the first measurement time instant affects the accuracy of clearance estimates if mixing is still incomplete. Moreover, measurement noise affects estimation precision which can be optimized by suitable choice of the sampling schedule and of the injected test dose. The aim of this study is to design two-sample bolus injection tests for measuring low plasma clearance rates with preassigned precision and with minimum amount of injected test substance. This paper provides equations for evaluating whether plasma clearance is sufficiently low to allow a monoexponential description of the plasma disappearance curve and for choosing the first sampling time instant. Closed form equations are proposed for determining the optimal test dose and the second sampling time. Result are derived for a particular heteroscedastic measurement noise description, and the problem of robustness with respect to interpatient variability of kinetic parameters is addressed. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.