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Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification

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Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification. / Barnett, H.Y.; Geys, H.; Jacobs, T. et al.
In: Statistics in Biopharmaceutical Research, Vol. 13, No. 1, 02.01.2021, p. 59-70.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Barnett, HY, Geys, H, Jacobs, T & Jaki, T 2021, 'Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification', Statistics in Biopharmaceutical Research, vol. 13, no. 1, pp. 59-70. https://doi.org/10.1080/19466315.2019.1701546

APA

Barnett, H. Y., Geys, H., Jacobs, T., & Jaki, T. (2021). Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification. Statistics in Biopharmaceutical Research, 13(1), 59-70. https://doi.org/10.1080/19466315.2019.1701546

Vancouver

Barnett HY, Geys H, Jacobs T, Jaki T. Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification. Statistics in Biopharmaceutical Research. 2021 Jan 2;13(1):59-70. Epub 2020 Jan 21. doi: 10.1080/19466315.2019.1701546

Author

Barnett, H.Y. ; Geys, H. ; Jacobs, T. et al. / Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification. In: Statistics in Biopharmaceutical Research. 2021 ; Vol. 13, No. 1. pp. 59-70.

Bibtex

@article{31c3b711dd74498c8bda6b28196eb5d6,
title = "Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification",
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.",
keywords = "Below limit of quantification, Kernel density estimation, Noncompartmental analysis, Pharmacokinetics",
author = "H.Y. Barnett and H. Geys and T. Jacobs and T. Jaki",
year = "2021",
month = jan,
day = "2",
doi = "10.1080/19466315.2019.1701546",
language = "English",
volume = "13",
pages = "59--70",
journal = "Statistics in Biopharmaceutical Research",
issn = "1946-6315",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Methods for Non-Compartmental Pharmacokinetic Analysis With Observations Below the Limit of Quantification

AU - Barnett, H.Y.

AU - Geys, H.

AU - Jacobs, T.

AU - Jaki, T.

PY - 2021/1/2

Y1 - 2021/1/2

N2 - 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.

AB - 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.

KW - Below limit of quantification

KW - Kernel density estimation

KW - Noncompartmental analysis

KW - Pharmacokinetics

U2 - 10.1080/19466315.2019.1701546

DO - 10.1080/19466315.2019.1701546

M3 - Journal article

VL - 13

SP - 59

EP - 70

JO - Statistics in Biopharmaceutical Research

JF - Statistics in Biopharmaceutical Research

SN - 1946-6315

IS - 1

ER -