Abstract

Pharmacokinetic (PK) studies are conducted to learn about the absorption, distribution, metabolism, and excretion processes of an externally administered compound by measuring its concentration in bodily tissue at a number of time points after administration. Two methods are available for this analysis: modeling and non-compartmental. When concentrations of the compound are low, they may be reported as below the limit of quantification (BLOQ). This article compares eight methods for dealing with BLOQ responses in the non-compartmental analysis framework for estimating the area under the concentrations versus time curve. These include simple methods that are currently used, maximum likelihood methods, and an algorithm that uses kernel density estimation to impute values for BLOQ responses. Performance is evaluated using simulations for a range of scenarios. We find that the kernel based method performs best for most situations. Supplementary materials for this article are available online.

摘要

进行药代动力学（PK）研究以通过在给药后多个时间点测量其在人体组织中的浓度来了解外用化合物的吸收，分布，代谢和排泄过程。有两种方法可用于此分析：建模和非隔室。当化合物的浓度较低时，可能报告为低于定量限（BLOQ）。本文比较了在非隔室分析框架中处理BLOQ响应的八种方法，以估计浓度与时间曲线下的面积。这些包括当前使用的简单方法，最大似然方法，以及使用核密度估计为BLOQ响应插值的算法。使用模拟针对各种场景评估性能。我们发现基于内核的方法在大多数情况下效果最佳。可在线获得本文的补充材料。